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Mondol RK, Millar EKA, Sowmya A, Meijering E. BioFusionNet: Deep Learning-Based Survival Risk Stratification in ER+ Breast Cancer Through Multifeature and Multimodal Data Fusion. IEEE J Biomed Health Inform 2024; 28:5290-5302. [PMID: 38913518 DOI: 10.1109/jbhi.2024.3418341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/26/2024]
Abstract
Breast cancer is a significant health concern affecting millions of women worldwide. Accurate survival risk stratification plays a crucial role in guiding personalised treatment decisions and improving patient outcomes. Here we present BioFusionNet, a deep learning framework that fuses image-derived features with genetic and clinical data to obtain a holistic profile and achieve survival risk stratification of ER+ breast cancer patients. We employ multiple self-supervised feature extractors (DINO and MoCoV3) pretrained on histopathological patches to capture detailed image features. These features are then fused by a variational autoencoder and fed to a self-attention network generating patient-level features. A co-dual-cross-attention mechanism combines the histopathological features with genetic data, enabling the model to capture the interplay between them. Additionally, clinical data is incorporated using a feed-forward network, further enhancing predictive performance and achieving comprehensive multimodal feature integration. Furthermore, we introduce a weighted Cox loss function, specifically designed to handle imbalanced survival data, which is a common challenge. Our model achieves a mean concordance index of 0.77 and a time-dependent area under the curve of 0.84, outperforming state-of-the-art methods. It predicts risk (high versus low) with prognostic significance for overall survival in univariate analysis (HR=2.99, 95% CI: 1.88-4.78, p 0.005), and maintains independent significance in multivariate analysis incorporating standard clinicopathological variables (HR=2.91, 95% CI: 1.80-4.68, p 0.005).
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Shioya A, Takata M, Kumagai M, Hoshi D, Han J, Oyama T, Haba Y, Morioka E, Inokuchi M, Noguchi M, Yamada S. Periarterial or perivenous invasion is an independent indicator of lymph node metastasis in invasive breast carcinoma of no special type. Pathol Res Pract 2024; 260:155407. [PMID: 38936093 DOI: 10.1016/j.prp.2024.155407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 06/05/2024] [Accepted: 06/12/2024] [Indexed: 06/29/2024]
Abstract
Pathological diagnosis of breast cancer often includes cases of lymph node metastases without lymphatic or lymphovascular invasion by the primary tumor. In this study, to resolve this discrepancy, we designed a sensitive method to detect lymphatic invasion and correlate it with lymph node metastasis. Elastica van Gieson (EVG) staining and D2-40 immunohistochemistry revealed the abundant distribution of lymphatic vessels around blood vessels in the mammary tissue in close proximity to the elastic fibers around the arteries and veins. Based on the histological location of the blood and lymphatic vessels, we hypothesized that, in breast cancer, perivascular invasion is similar to lymphatic invasion and correlates with the presence of lymph node metastasis. Using EVG staining, perivascular invasion was histologically classified into periarterial invasion (periA), perivenous invasion (periV), and periarterial or perivenous invasion (periA/V). We tested our method and compared it to other methods commonly used for identifying lymphatic invasion in 105 patients with invasive breast carcinoma of no special type (IBC-NST) who received minimal preoperative therapy. The correlation between perivascular invasion and lymph node metastasis in these patients was statistically analyzed, including findings related to lymphatic invasion, such as retractile artifacts and perineural invasion. PeriA, periV, and periA/V showed significant correlations with lymph node metastasis. PeriA/V had high sensitivity and negative predictive value. The odds ratio (OR) for periV was significantly high in the univariate analysis, while the ORs for periA/V, retraction artifacts, and perineural invasion were significantly high in both the univariate and multivariate analyses. In particular, periA/V revealed a strong correlation with lymph node metastasis (OR: 61.8). These findings indicate that the IBC-NST periA/V ratio is a sensitive pointer of lymphatic invasion and could be an independent and reliable indicator of lymph node metastasis.
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Affiliation(s)
- Akihiro Shioya
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, Japan.
| | - Mao Takata
- Department of Pathology, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, Japan
| | - Motona Kumagai
- Department of Pathophysiological and Experimental Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, Japan
| | - Daisuke Hoshi
- Department of Oncologic Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, Japan
| | - Jia Han
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, Japan
| | - Takeru Oyama
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, Japan
| | - Yusuke Haba
- Department of Breast and Endocrine Surgery, Breast Center, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, Japan
| | - Emi Morioka
- Department of Breast and Endocrine Surgery, Breast Center, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, Japan
| | - Masafumi Inokuchi
- Department of Breast and Endocrine Surgery, Breast Center, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, Japan
| | - Masakuni Noguchi
- Department of Breast and Endocrine Surgery, Breast Center, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, Japan
| | - Sohsuke Yamada
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, Japan
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Gunes G, Crivellaro P, Muradali D. Management of MRI-Detected Benign Internal Mammary Lymph Nodes. Indian J Radiol Imaging 2022; 32:197-204. [PMID: 35924122 PMCID: PMC9340169 DOI: 10.1055/s-0042-1750180] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Introduction In this retrospective study, we aimed to evaluate benign internal mammary lymph nodes (IMLNs) in terms of frequency, number, size, long axis/short axis (L/S) ratio, intercostal location, presence of fatty hilum, and stability using breast magnetic resonance imaging (MRI) and discuss the findings by reviewing existing literature. Methods This single-center study consisted of 130 women between the ages of 24 and 76 years, who had at least two breast MRI examinations in our institution, with the latest exam performed between January 1, 2019 and November 1, 2019, were eligible for the study. MRIs of the study group were independently reviewed by two radiologists. Results IMLN was detected in 31.1% of the 427 MRIs, with a total number of 256 nodes. The most common indication for breast MRI was high-risk screening (66.2%). The median number of nodes per patient was 1 (range: 1-6). The median follow-up time was 19.5 months (range: 6-141 months). None of these benign nodes showed significant interval growth. Mean L/R ratio of the nodes was 1.9. One hundred and four nodes ( n = 104, 40.6%) had a L/S ratio less than 2 and 43.2% ( n = 45) of the nodes with a L/S ratio less than 2, had a long axis measuring less than or equal to 3mm. IMLN of patients with breast implants had the largest mean long axis. The fatty hilum was identified in 34.3% ( n = 68) of the 256 nodes. The size of the lymph nodes where fatty hilum was visualized was significantly larger than the ones where fatty hilum was not visualized ( p < 0.001). Fatty hilum could be visualized in only 2.7% of the nodes with a long axis smaller than 3 mm. Conclusion IMLN is a frequent finding on breast MRI. We have shown that benign IMLNs might be large sized in specific cases like patients with breast implants. When small sized (≤3mm), they are more likely to be rounded (L/S ratio <2). The fatty hilum that is a feature of benignity might not be visualized in nodes less than or equal to3mm.
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Affiliation(s)
- Gozde Gunes
- Department of Radiology, Baskent University Hospital, Çankaya/Ankara, Turkey
| | - Priscila Crivellaro
- Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada
| | - Derek Muradali
- Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada
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Modeling Tumor: Lymphatic Interactions in Lymphatic Metastasis of Triple Negative Breast Cancer. Cancers (Basel) 2021; 13:cancers13236044. [PMID: 34885152 PMCID: PMC8656640 DOI: 10.3390/cancers13236044] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 11/24/2021] [Accepted: 11/26/2021] [Indexed: 12/04/2022] Open
Abstract
Simple Summary Lymphatic metastasis is a critical prognostic factor of breast cancer aggressiveness and patient survival. Since existing therapeutic approaches have shown limited efficacy, new strategies to identify effective therapeutic targets for reducing breast cancer lymphatic metastasis are needed. We have used novel culture chambers, designed and fabricated by our group, to develop 3D models in which we can study spat ial interactions between breast cancer cells and lymphatic cells as they occur in real-time. This approach provides information on the complex cell–cell interactions involved in lymphatic metastasis of breast cancers. Factors in the secretome of the lymphatic cells promote invasive outgrowths from 3D cultures of breast cancer cells, suggesting that targeting interactions between breast cancer cells and lymphatic cells could be a potential therapeutic approach for the prevention of lymphatic metastasis. Abstract Breast cancer frequently metastasizes to lymphatics and the presence of breast cancer cells in regional lymph nodes is an important prognostic factor. Delineating the mechanisms by which breast cancer cells disseminate and spatiotemporal aspects of interactions between breast cancer cells and lymphatics is needed to design new therapies to prevent lymphatic metastases. As triple-negative breast cancer (TNBC) has a high incidence of lymphatic metastasis, we used a three-dimensional (3D) coculture model of human TNBC cells and human microvascular lymphatic endothelial cells (LECs) to analyze TNBC:LEC interactions. Non-invasive analyses such as live-cell imaging in real-time and collection of conditioned media for secretomic analysis were facilitated by our novel microfluidic chambers. The volumes of 3D structures formed in TNBC:LEC cocultures are greater than that of 3D structures formed by either LEC or TNBC monocultures. Over 4 days of culture there is an increase in multicellular invasive outgrowths from TNBC spheroids and an association of TNBC spheroids with LEC networks. The increase in invasive phenotype also occurred when TNBC spheroids were cultured in LEC-conditioned media and in wells linked to ones containing LEC networks. Our results suggest that modeling spatiotemporal interactions between TNBC and LECs may reveal paracrine signaling that could be targeted to reduce lymphatic metastasis.
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Predictive modelling of level IIb lymph node metastasis in oral squamous cell carcinoma. Sci Rep 2021; 11:17562. [PMID: 34475441 PMCID: PMC8413325 DOI: 10.1038/s41598-021-96827-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 08/12/2021] [Indexed: 02/07/2023] Open
Abstract
The aim of the present study was to examine the conditions, characteristics, and risk factors of level IIb lymph node metastases in oral squamous cell carcinoma and to formulate surgical criteria for level IIb lymph node dissection. We analyzed clinical and pathological records for 541 oral squamous carcinoma patients in relation to level IIb metastasis. Univariate and multivariate analyses were performed to detect risk factors for level IIb lymph node metastasis; a predictive model was built based on multivariate analysis and tested in a validation group. Univariate and multivariate analyses using the training group indicated that level IIa metastasis and Lymphovascular permeation (LVP) were two independent risk factors for level IIb lymph node metastasis. This model was built and tested in a validation group, the area under the curve being 0.697 (P < .0.001). The model's sensitivity was 66.7% and specificity was 77.4%. Nomogram incorporating validated variables was developed for level IIb metastasis prediction. Expected survival probabilites were analysed to specify significance of model's variable on patients' overall survival and recurrence. Level IIb dissection should be performed in patients with level IIa metastasis and LVP. However, thorough consideration of the oncologic safety of omitting level IIb dissection is compulsory.
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Prognostic Role of Lymphovascular Invasion in Patients with Early Breast Cancer. Indian J Surg Oncol 2021; 12:671-677. [DOI: 10.1007/s13193-021-01367-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 06/02/2021] [Indexed: 11/26/2022] Open
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Rupa R, Thushara R, Swathigha S, Athira R, Meena N, Cherian MP. Diffusion weighted imaging in breast cancer - Can it be a noninvasive predictor of nuclear grade? Indian J Radiol Imaging 2020; 30:13-19. [PMID: 32476745 PMCID: PMC7240885 DOI: 10.4103/ijri.ijri_97_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 07/12/2019] [Accepted: 10/30/2019] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND DWI and ADC values are noninvasive MRI techniques, which provide quantitative information about tumor heterogeneity. AIM To determine the minimum and mean ADC values in breast carcinoma and to correlate ADC values with various prognostic factors. SETTINGS AND DESIGN Prospective observational study. MATERIALS AND METHODS Fifty-five patients with biopsy-proven breast carcinoma were included in this study. MRI with DWI was performed with Siemens 3T Skyra scanner. ADC values were measured by placing regions of interest (ROIs) within the targeted lesions on ADC maps manually. The histopathological and immunohistochemical analysis of surgical specimen was done to determine the prognostic factors. STATISTICAL ANALYSIS Students T test and ANOVA were used to study the difference in ADC between two groups. Pearson correlation coefficient was used to quantify the correlation between ADC values and prognostic factors. RESULTS Lower grade (grade I) breast carcinoma had a significantly high ADC value as compared to higher grade carcinoma (grade II and III). For differentiating Grade I tumors from grade II and III, a minimum ADC cut-off value was 0.79 × 10-3 mm2/sec (83% sensitivity and 84% specificity) and a mean ADC cut-off value was 0.82 × 10-3 mm2/sec (83% sensitivity and 71% specificity) was derived. There was no significant correlation between ADC and other prognostic factors. CONCLUSION ADC values can be used to differentiate lower grade breast carcinoma (grade I) from higher grades (grade II and III). Minimum ADC values are more accurate in predicting the grade of the breast tumor than mean ADC value.
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Affiliation(s)
- R Rupa
- Division of Breast Imaging, Department of Diagnostic and Interventional Radiology, Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India
| | - R Thushara
- Division of Breast Imaging, Department of Diagnostic and Interventional Radiology, Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India
| | - S Swathigha
- Division of Breast Imaging, Department of Diagnostic and Interventional Radiology, Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India
| | - R Athira
- Division of Breast Imaging, Department of Diagnostic and Interventional Radiology, Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India
| | - N Meena
- Division of Breast Imaging, Department of Diagnostic and Interventional Radiology, Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India
| | - Mathew P Cherian
- Division of Breast Imaging, Department of Diagnostic and Interventional Radiology, Kovai Medical Center and Hospital, Coimbatore, Tamil Nadu, India
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Danzig MR, Mallin K, McKiernan JM, Stadler WM, Sridhar SS, Morgan TM, Bochner BH, Lee CT. Prognostic importance of lymphovascular invasion in urothelial carcinoma of the renal pelvis. Cancer 2018; 124:2507-2514. [PMID: 29624636 DOI: 10.1002/cncr.31372] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2017] [Revised: 02/03/2018] [Accepted: 02/20/2018] [Indexed: 11/08/2022]
Abstract
BACKGROUND The current study was conducted to assess the impact of lymphovascular invasion on the survival of patients with urothelial carcinoma of the renal pelvis. METHODS Patients with urothelial carcinoma of the renal pelvis who underwent radical nephroureterectomy from 2010 through 2015 were identified in the National Cancer Data Base. Patients were characterized according to demographic and clinical factors, including pathologic tumor stage and lymphovascular invasion. Associations with overall survival were assessed through proportional hazards regression analysis. RESULTS A total of 4177 patients were identified; 1576 had lymphovascular invasion. Patients with T3 disease and lymphovascular invasion had 5-year survival that was significantly worse than that of patients with T3 disease without lymphovascular invasion (34.7% vs 52.6; P < .001 by the log-rank test), and approached that of patients with T4 disease without lymphovascular invasion (34.7% vs 26.5%; P = .002). On multivariate analysis controlling for age, comorbidities, grade, lymph node status, surgical margin status, race, sex, and chemotherapy administration, patients with T3 disease and lymphovascular invasion also were found to have significantly worse survival compared with patients with T3 disease without lymphovascular invasion (hazard ratio, 1.7; 95% confidence interval, 1.4-1.91). CONCLUSIONS Lymphovascular invasion status is a key prognostic marker that can stratify the risk of patients with pT3 upper tract urothelial carcinoma further. Patients with this pathologic feature should be carefully considered for clinical trials exploring existing and novel therapies. Cancer 2018;124:2507-14. © 2018 American Cancer Society.
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Affiliation(s)
- Matthew R Danzig
- Division of Urology, Department of Surgery, University of Colorado, Aurora, Colorado
| | - Katherine Mallin
- American College of Surgeons, Commission on Cancer, Chicago, Illinois
| | | | - Walter M Stadler
- Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois
| | - Srikala S Sridhar
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto, Ontario, Canada
| | - Todd M Morgan
- Department of Urology, University of Michigan, Ann Arbor, Michigan
| | - Bernard H Bochner
- Department of Urology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Cheryl T Lee
- Department of Urology, The Ohio State University, Columbus, Ohio
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Lee SA, Lee HM, Lee HW, Yang BS, Park JT, Ahn SG, Jeong J, Kim SI. Risk Factors for a False-Negative Result of Sentinel Node Biopsy in Patients with Clinically Node-Negative Breast Cancer. Cancer Res Treat 2017; 50:625-633. [PMID: 28759990 PMCID: PMC6056988 DOI: 10.4143/crt.2017.089] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Accepted: 06/20/2017] [Indexed: 11/21/2022] Open
Abstract
Purpose Although sentinel lymph node biopsy (SLNB) can accurately represent the axillary lymph node (ALN) status, the false-negative rate (FNR) of SLNB is the main concern in the patients who receive SLNB alone instead of ALN dissection (ALND). Materials and Methods We analyzed 1,886 patientswho underwent ALND after negative results of SLNB,retrospectively. A logistic regression analysis was used to identify risk factors associated with a falsenegative (FN) result. Cox regression model was used to estimate the hazard ratio of factors affecting disease-free survival (DFS). Results Tumor located in the upper outer portion of the breast, lymphovascular invasion, suspicious node in imaging assessment and less than three sentinel lymph nodes (SLNs) were significant independent risk factors for FN in SLNB conferring an adjusted odds ratio of 2.10 (95% confidence interval [CI], 1.30 to 3.39), 2.69 (95% CI, 1.47 to 4.91), 2.59 (95% CI, 1.62 to 4.14), and 2.39 (95% CI, 1.45 to 3.95), respectively. The prognostic factors affecting DFS were tumor size larger than 2 cm (hazard ratio [HR], 1.86; 95% CI, 1.17 to 2.96) and FN of SLNB (HR, 2.51; 95% CI, 1.42 to 4.42) in SLN-negative group (FN and true-negative), but in ALN-positive group (FN and true-positive), FN of SLNB (HR, 0.64; 95% CI, 0.33 to 1.25) did not affect DFS. Conclusion In patients with risk factors for a FN such as suspicious node in imaging assessment, upper outer breast cancer, less than three harvested nodes, we need attention to find another metastatic focus in non-SLNs during the operation. It may contribute to provide an exact prognosis and optimizing adjuvant treatments.
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Affiliation(s)
- Seung Ah Lee
- Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Korea.,Department of Medicine, Graduate School, Yonsei University, Seoul, Korea
| | - Hak Min Lee
- Department of Surgery, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Gangneung, Korea
| | - Hak Woo Lee
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Ban Seok Yang
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jong Tae Park
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Gwe Ahn
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Joon Jeong
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Il Kim
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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Klahan S, Wong HSC, Tu SH, Chou WH, Zhang YF, Ho TF, Liu CY, Yih SY, Lu HF, Chen SCC, Huang CC, Chang WC. Identification of genes and pathways related to lymphovascular invasion in breast cancer patients: A bioinformatics analysis of gene expression profiles. Tumour Biol 2017. [PMID: 28651487 DOI: 10.1177/1010428317705573] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Surgery is the most effective treatment for breast cancer patients. However, some patients developed recurrence and distant metastasis after surgery. Adjuvant therapy is considered for high-risk patients depending on several prognostic markers, and lymphovascular invasion has become one of such prognostic markers that help physicians to identify the risk for distant metastasis and recurrence. However, the mechanism of lymphovascular invasion in breast cancer remains unknown. This study aims to unveil the genes and pathways that may involve in lymphovascular invasion in breast cancer. In total, 108 breast cancer samples were collected during surgery and microarray analysis was performed. Significance analysis of the microarrays and limma package for R were used to examine differentially expressed genes between lymphovascular invasion-positive and lymphovascular invasion-negative cases. Network and pathway analyses were mapped using the Ingenuity Pathway Analysis and the Database for Annotation, Visualization and Integrated Discovery. In total, 86 differentially expressed genes, including 37 downregulated genes and 49 upregulated genes were identified in lymphovascular invasion-positive patients. Among these genes, TNFSF11, IL6ST, and EPAS1 play important roles in cytokine-receptor interaction, which is the most enriched pathway related to lymphovascular invasion. Moreover, the results also suggested that an imbalance between extracellular matrix components and tumor micro-environment could induce lymphovascular invasion. Our study evaluated the underlying mechanisms of lymphovascular invasion, which may further help to assess the risk of breast cancer progression and identify potential targets of adjuvant treatment.
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Affiliation(s)
- Sukhontip Klahan
- 1 Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University
| | - Henry Sung-Ching Wong
- 1 Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University.,2 Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Shih-Hsin Tu
- 3 Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,4 Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan
| | - Wan-Hsuan Chou
- 2 Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Yan-Feng Zhang
- 5 HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA
| | - Thien-Fiew Ho
- 6 Department of Surgery, Cathay General Hospital Sijhih, New Taipei City, Taiwan
| | - Chih-Yi Liu
- 7 Department of Pathology, Cathay General Hospital Sijhih, New Taipei City, Taiwan
| | - Shih-Ying Yih
- 8 Department of Hematology and Oncology, Cathay General Hospital Sijhih, New Taipei City, Taiwan
| | - Hsing Fang Lu
- 1 Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University
| | - Sean Chun-Chang Chen
- 9 Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University
| | - Chi-Cheng Huang
- 3 Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,10 Breast Center, Cathay General Hospital, Taipei, Taiwan.,11 School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan
| | - Wei-Chiao Chang
- 1 Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University.,2 Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.,12 Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,13 Department of Pharmacy, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.,14 Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan
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12
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Ozen A, Altinay S, Ekmekcioglu O, Albayrak R, Muhammedoglu A, Yigitbas H, Bastug E, Celik A. Dual-Time 18F-FDG PET/CT Imaging in Initial Locoregional Staging of Breast Carcinoma: Comparison with Conventional Imaging and Pathological Prognostic Factors. Indian J Surg 2016; 78:382-389. [PMID: 27994334 DOI: 10.1007/s12262-016-1486-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Accepted: 04/18/2016] [Indexed: 11/28/2022] Open
Abstract
The aims of this retrospective study were to consider the diagnostic role of dual-time 18F-fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET/CT) in detection of breast carcinoma and axillary lymph node (ALN) status and to evaluate the primary tumor 18F-FDG uptake pattern. Preoperative staging was performed by 18F-FDG PET/CT in 78 female patients with breast carcinoma. Conventional imaging results were evaluated by breast magnetic resonance imaging (MRI) of 79 lesions in 78 patients, bilateral mammography (MMG) of 40 lesions in 40 patients, and breast ultrasonography (USG) of 47 lesions in 46 patients. The primary tumor detection rate using 18F-FDG PET/CT was higher than those using MRI, USG, and MMG. The sensitivity and specificity of 18F-FDG PET/CT scans for detecting multifocality were higher than those of MRI. The specificity of ALN metastasis detection with MRI was higher than that with 18F-FDG PET/CT, but 18F-FDG PET/CT had higher sensitivity. Higher 18F-FDG uptake levels were detected in patients with ALN metastasis, histologic grade 3, estrogen-progesterone-negative receptor status, lymphatic invasion, and moderate to poor prognostic groups. There was no statistical difference for the retention index in categorical pathological parameters except for progesterone-negative status. In conclusion, 18F-FDG PET/CT scans may be a valuable imaging technique for evaluating primary tumor and axillary status in staging breast carcinoma and 18F-FDG uptake may be a prognostic factor that indicates aggressive tumor biology and poor prognosis. Dual-time imaging in breast carcinoma staging may not be used for predicting pathological criteria and the aggressiveness of primary lesions.
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Affiliation(s)
- Aynur Ozen
- Department of Nuclear Medicine, Bagcilar Training and Research Hospital, Istanbul, Turkey
| | - Serdar Altinay
- Department of Pathology, Bagcilar Training and Research Hospital, Istanbul, Turkey
| | - Ozgul Ekmekcioglu
- Department of Nuclear Medicine, Bagcilar Training and Research Hospital, Istanbul, Turkey
| | - Ramazan Albayrak
- Department of Radiology, Bagcilar Training and Research Hospital, Istanbul, Turkey
| | - Ali Muhammedoglu
- Department of Pathology, Bagcilar Training and Research Hospital, Istanbul, Turkey
| | - Hakan Yigitbas
- Department of General Surgery, Bagcilar Training and Research Hospital, Istanbul, Turkey
| | - Eylem Bastug
- Department of Nuclear Medicine, Bagcilar Training and Research Hospital, Istanbul, Turkey
| | - Atilla Celik
- Department of General Surgery, Bagcilar Training and Research Hospital, Istanbul, Turkey
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Guvenc I, Akay S, Ince S, Yildiz R, Kilbas Z, Oysul FG, Tasar M. Apparent diffusion coefficient value in invasive ductal carcinoma at 3.0 Tesla: is it correlated with prognostic factors? Br J Radiol 2016; 89:20150614. [PMID: 26853508 DOI: 10.1259/bjr.20150614] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
OBJECTIVE To investigate the correlation between apparent diffusion coefficient (ADC) values and prognostic factors in patients with invasive ductal carcinoma (IDC). METHODS 48 lesions belonging to 47 patients with histopathologically proven IDC were examined using conventional MR and diffusion-weighted imaging at a 3.0-T system. All of the patients had modified radical mastectomies or breast-sparing surgery plus axillary lymph node dissection. The ADC values acquired from the ADC maps consisted of six different b-values (0, 50, 100, 500, 1000 and 1500 s mm(-2)) and were compared with the patients' ages, tumour size, histological grade of the lesions, tumour localization, lesions' distance to skin surface and nipples, the existence of axillary lymph node involvement, the number of involved axillary lymph nodes, oestrogen/progesterone receptor status, peritumoral lymphovascular invasion status and the existence of human epidermal growth factor 2 (c-erbB-2) overexpression. RESULTS A statistically significant relationship was found regarding axillary lymph node involvement (p = 0.027), and oestrogen/progesterone receptor status (p = 0.013). No significant relationship was detected regarding other prognostic factors (p > 0.05). CONCLUSION Among various prognostic factors, ADC values were significantly correlated with only axillary lymph node positivity and oestrogen/progesterone receptor status. ADVANCES IN KNOWLEDGE In the present study, the relationship between ADC values of IDC lesions that are acquired at a high magnetic field (3.0 T) system by using multiple b-values and some specific prognostic factors that were not evaluated before in the medical literature was investigated.
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Affiliation(s)
- Inanc Guvenc
- 1 Department of Radiology, Gulhane Military Medical School, Ankara, Turkey
| | - Sinan Akay
- 2 Department of Radiology, Sirnak Military Hospital, Sirnak, Turkey
| | - Selami Ince
- 1 Department of Radiology, Gulhane Military Medical School, Ankara, Turkey
| | - Ramazan Yildiz
- 3 Department of General Surgery, Gulhane Military Medical School, Ankara, Turkey
| | - Zafer Kilbas
- 3 Department of General Surgery, Gulhane Military Medical School, Ankara, Turkey
| | - Fahrettin G Oysul
- 4 Department of Public Health, Gulhane Military Medical School, Ankara, Turkey
| | - Mustafa Tasar
- 1 Department of Radiology, Gulhane Military Medical School, Ankara, Turkey
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14
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Huang Q, Luo K, Chen C, Wang G, Jin J, Kong M, Li B, Liu Q, Li J, Rong T, Chen H, Zhang L, Chen Y, Zhu C, Zheng B, Wen J, Zheng Y, Tan Z, Xie X, Yang H, Fu J. Identification and Validation of Lymphovascular Invasion as a Prognostic and Staging Factor in Node-Negative Esophageal Squamous Cell Carcinoma. J Thorac Oncol 2016; 11:583-92. [PMID: 26792626 DOI: 10.1016/j.jtho.2015.12.109] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Revised: 12/06/2015] [Accepted: 12/15/2015] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Lymphovascular invasion (LVI) is a histopathological feature that is associated with an increased risk for micrometastasis. The aim of this study was to determine the prognostic and staging value of LVI among patients with esophageal squamous cell carcinoma (ESCC) undergoing esophagectomy. METHODS A prospective database of patients with ESCC was used to retrospectively analyze 666 cases to identify the relationship between LVI and survival, and to evaluate predictive accuracy of prognosis after combining LVI and the tumor, node, and metastasis (TNM) system. Pathological slides were reassessed by gastrointestinal pathologists according to the strict criteria; 1000-bootstrap resampling was used for internal validation, and 222 cases from an independent multicenter database were used for external validation. RESULTS LVI was present in 33.8% of patients, and the proportion increased with advancing T and N classification. LVI was an independent predictor of unfavorable disease-specific survival (DSS) (hazard ratio = 1.59, 95% confidence interval: 1.30-1.94) and disease-free survival (DFS) (hazard ratio = 1.62, 95% confidence interval: 1.32-1.98) after T classification. Among node-negative patients, LVI and T classification were two independent predictors of DSS and DFS (p < 0.001). The risk score model combing LVI and T classification improved the predictive accuracy of the TNM system for DSS and DFS by 3.5% and 4.8%, respectively (p < 0.001). The external validation showed congruent results. The DSS of TxN0MO disease with LVI was similar to the DSS of TxN1M0 (both p > 0.05). In contrast, LVI was not associated with DSS or DFS among node-positive patients. CONCLUSIONS The independent prognostic significance of LVI existed only in node-negative patients with ESCC, and the combination of LVI and the TNM system enhanced the predictive accuracy of prognosis. After confirmation, node-negative patients with LVI might be considered for upstaging in pathological staging.
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Affiliation(s)
- Qingyuan Huang
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China
| | - Kongjia Luo
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China
| | - Chun Chen
- Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
| | - Geng Wang
- Cancer Hospital of Shantou University Medical College, Shantou, People's Republic of China
| | - Jietian Jin
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Min Kong
- Taizhou Hospital, Taizhou, People's Republic of China
| | - Bifeng Li
- Fujian Medical University Union Hospital, Fuzhou, People's Republic of China; Xiamen Traditional Hospital, Xiamen, People's Republic of China
| | - Qianwen Liu
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China
| | - Jinhui Li
- School of Public Health, the University of Hong Kong, Hong Kong, People's Republic of China
| | - Tiehua Rong
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China
| | - Haiquan Chen
- Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Lanjun Zhang
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China
| | - Yuping Chen
- Cancer Hospital of Shantou University Medical College, Shantou, People's Republic of China
| | - Chengchu Zhu
- Taizhou Hospital, Taizhou, People's Republic of China
| | - Bin Zheng
- Fujian Medical University Union Hospital, Fuzhou, People's Republic of China
| | - Jing Wen
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China
| | - Yuzhen Zheng
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China
| | - Zihui Tan
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China
| | - Xiuying Xie
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China
| | - Hong Yang
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China
| | - Jianhua Fu
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; Guangdong Esophageal Cancer Institute, Guangzhou, People's Republic of China.
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Fujii T, Yajima R, Morita H, Hirakata T, Miyamoto T, Fujisawa T, Tsutsumi S, Ynagita Y, Iijima M, Kuwano H. Impact of Vascular Invasion of a Primary Tumor as a Strong Risk Factor for Disease Recurrence in Patients with Node-Positive Breast Cancer. Am Surg 2015. [DOI: 10.1177/000313481508100537] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The presence of lymph node metastasis is considered to be the most significant indicator of prognosis. However, in some cases with node-positive breast cancer, cancer cell dissemination is localized to the lymphatic systems. It is, therefore, important to develop selection criteria for strong adjuvant therapy in patients with node-positive breast cancer. This study was undertaken to evaluate the presence of vascular invasion that may reflect systemic disease as a predictor of disease recurrence in node-positive breast cancer. We retrospectively evaluated the cases of 134 consecutive female patients with breast cancer with lymph node metastasis who underwent radical breast operations. We examined the relationship between recurrence and clinicopathological factors, particularly vascular invasion. The presence of vascular invasion was found to be significant in a univariate analysis. The presence of vascular invasion was the independent risk factor in a multivariate analysis. Among the 66 patients without vascular invasion, four (6.1%) had disease recurrence. On the other hand, among the 68 patients with vascular invasion, 15 (22.1%) had a recurrence. It is interesting to note that despite the presence of lymph node metastasis, the group without vascular invasion had few patients with distant metastases. Our results suggest that the presence of vascular invasion could be an indicator of high biological aggressiveness and may be a strong prognostic factor for node-positive breast cancer.
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Affiliation(s)
- Takaaki Fujii
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan and the Departments of
| | - Reina Yajima
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan and the Departments of
| | - Hiroki Morita
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan and the Departments of
| | | | | | | | - Soichi Tsutsumi
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan and the Departments of
| | - Yasuhiro Ynagita
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan and the Departments of
| | - Misa Iijima
- Pathology, Gunma Prefectural Cancer Center, Ota, Gunma, Japan
| | - Hiroyuki Kuwano
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan and the Departments of
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16
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Prognostic impact of perineural invasion and lymphovascular invasion in advanced stage oral squamous cell carcinoma. Int J Oral Maxillofac Surg 2015; 44:23-8. [DOI: 10.1016/j.ijom.2014.10.006] [Citation(s) in RCA: 87] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2014] [Revised: 07/30/2014] [Accepted: 10/03/2014] [Indexed: 11/22/2022]
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17
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Mohammed RAA, Menon S, Martin SG, Green AR, Paish EC, Ellis IO. Prognostic significance of lymphatic invasion in lymph node-positive breast carcinoma: findings from a large case series with long-term follow-up using immunohistochemical endothelial marker. Mod Pathol 2014; 27:1568-77. [PMID: 24762542 DOI: 10.1038/modpathol.2014.60] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Accepted: 03/12/2014] [Indexed: 01/26/2023]
Abstract
The poor prognostic significance of lymphatic invasion (LI) in breast carcinoma (BC) as a whole and in lymph node (LN)-negative patients in particular has been recognized in several studies; however, its prognostic role in LN-positive patients is still questionable. Aim of the current study was to assess prognostic role of LI in LN-positive BC specimens. Sections from non-selected 557 LN-positive BC specimens were stained with antibody to podoplanin/D2-40. LI was identified and correlated with clinicopathological features and patients' outcome. Twenty-year overall survival (OS), disease-free interval (DFI), and development of distant metastasis (DM) or recurrence were known for all patients. LI was detected in 262/557 (47%) of specimens ranging from 1 to 350 lesion per tumor section. Its presence was associated with higher grade tumors (P<0.0001), negative hormonal receptors (P<0.0001), high HER-2 expression (P=0.006), and with increased number of positive LNs (P=0.019). In the whole LN-positive BC, presence of LI was a poor prognostic factor for OS, DFI, and development of DM both in univariate and in multivariate analysis. In further stratification of patients, LI was associated with poorer prognosis in patients with single positive LN and not in patients with >1 positive LN. In T1N1 stage, LI was highly associated with poor OS (P=0.002), DFI (P<0.0001), and DM (P<0.0001). In T2N1 patients, LI was associated only with poorer DFI (P=0.037) but not with death or DM. In the two former patient groups, LI lost significance in multivariate analysis. In conclusion, LI is a poor prognostic factor in LN-positive BC particularly for patients having single positive LN. LI therefore would add further prognostic significance when considered in treatment in those patients. We recommend incorporation of LI in breast carcinoma staging and in prognostic indices.
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Affiliation(s)
- Rabab A A Mohammed
- Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Sindhu Menon
- Department of Histopathology, Royal Derby Hospital, Derby, UK
| | - Stewart G Martin
- Department of Clinical Oncology, University of Nottingham, University Hospitals, Nottingham, UK
| | - Andrew R Green
- Department of Histopathology, University of Nottingham, University Hospitals, Nottingham, UK
| | - Emma C Paish
- Department of Histopathology, University of Nottingham, University Hospitals, Nottingham, UK
| | - Ian O Ellis
- Department of Histopathology, University of Nottingham, University Hospitals, Nottingham, UK
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Gangi A, Mirocha J, Leong T, Giuliano AE. Triple-Negative Breast Cancer is Not Associated with Increased Likelihood of Nodal Metastases. Ann Surg Oncol 2014; 21:4098-103. [DOI: 10.1245/s10434-014-3989-7] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Indexed: 11/18/2022]
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19
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Yajima R, Fujii T, Yanagita Y, Fujisawa T, Miyamoto T, Hirakata T, Tsutsumi S, Iijima M, Kuwano H. Prognostic Value of Extracapsular Invasion of Axillary Lymph Nodes Combined with Peritumoral Vascular Invasion in Patients with Breast Cancer. Ann Surg Oncol 2014; 22:52-8. [DOI: 10.1245/s10434-014-3941-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2014] [Indexed: 12/30/2022]
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20
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Post-mastectomy radiotherapy benefits subgroups of breast cancer patients with T1-2 tumor and 1-3 axillary lymph node(s) metastasis. Radiol Oncol 2014; 48:314-22. [PMID: 25177247 PMCID: PMC4110089 DOI: 10.2478/raon-2013-0085] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2013] [Accepted: 10/20/2013] [Indexed: 01/01/2023] Open
Abstract
Background To determine the role of postmastectomy radiotherapy (PMRT) in breast cancer patients with T1–2 and N1 disease. Patients and methods. A total of 207 postmastectomy women were enrolled. The 5-year Kaplan-Meier estimates of locoregional recurrence rate (LRR), distant recurrence rate (DRR) and overall survival (OS) were analyzed by different tumor characteristics. Multivariate analyses were performed using Cox proportional hazards modeling. Results With median follow-up 59.5 months, the 5-year LRR, DRR and OS were 9.1%, 20.3% and 84.4%, respectively. On univariate analysis, age < 40 years old (p = 0.003) and Her-2/neu over-expression (p = 0.016) were associated with higher LRR, whereas presence of LVI significantly predicted higher DRR (p = 0.026). Negative estrogen status (p = 0.033), Her-2/neu overexpression (p = 0.001) and LVI (p = 0.01) were significantly correlated with worse OS. PMRT didn’t prove to reduce 5-year LRR (p = 0.107), as well as 5-year OS (p = 0.918). In subgroup analysis, PMRT showed significant benefits of improvement LRR and OS in patients with positive LVI. Conclusions For patients with T1–2 and N1 stage breast cancer, PMRT can decrease locoregional recurrence and increase overall survival only in patients with lymphovascular invasion.
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Kwon HJ, Kim SG, Chun JM, Lee WK, Hwang YJ. Prognostic factors in patients with middle and distal bile duct cancers. World J Gastroenterol 2014; 20:6658-6665. [PMID: 24914391 PMCID: PMC4047355 DOI: 10.3748/wjg.v20.i21.6658] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2013] [Revised: 02/25/2014] [Accepted: 03/13/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify the influence of the surgery type and prognostic factors in middle and distal bile duct cancers.
METHODS: Between August 1990 and June 2011, data regarding the clinicopathological factors of 194 patients with surgical and pathological confirmation were collected. A total of 133 patients underwent resections (R0, R1, R2; n = 102, 24, 7), whereas 61 patients underwent nonresectional surgery. Either pancreaticoduodenectomy (PD) or bile duct resection (BDR) was selected according to the sites of tumors and co-morbidities of the patients after confirming resection margin by the frozen histology in all cases. Univariate and multivariate analyses of clinicopathologic factors were performed, utilizing the Kaplan-Meyer method and Cox hazard regression analysis.
RESULTS: The overall 5-year survival rate for the 133 patients who underwent resection (R0, R1, and R2) was 41.2%, whereas no patients survived longer than 3 years among the 61 patient who underwent nonresectional surgeries. The 5-year survival rate of the patients who underwent a PD (n = 90) was higher than the rate of those who underwent BDR (n = 43), although the difference was not statistically significant (46.6% vs 30.0% P = 0.105). However, PD had a higher rate of R0 resection than BDR (90.0% vs 48.8%, P < 0.0001). If R0 resection was achieved, PD and BDR showed similar survival rates (49.4% vs 46.5% P = 0.762). The 5-year survival rates of R0 and R1 resections were not significantly different (49.0% vs 21.0% P = 0.132), but R2 resections had lower survival (0%, P = 0.0001). Although positive lymph node, presence of perineural invasion, presence of lymphovascular invasion (LVI), 7th AJCC-UICC tumor node metastasis (TNM) stage, and involvement of resection margin were significant prognostic factors in univariate analysis, multivariate analysis identified only TNM stage and LVI as independent prognostic factors.
CONCLUSION: PD had a greater likelihood of curative resection and R1 resection might have some positive impact. The TNM stage and LVI were independent prognostic factors.
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22
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Kim H, Kim M, Kwak C, Kim HH, Ku JH. Prognostic significance of lymphovascular invasion in radical cystectomy on patients with bladder cancer: a systematic review and meta-analysis. PLoS One 2014; 9:e89259. [PMID: 24586637 PMCID: PMC3931717 DOI: 10.1371/journal.pone.0089259] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Accepted: 01/16/2014] [Indexed: 12/26/2022] Open
Abstract
Purpose The objective of the present study was to conduct a systematic review and meta-analysis of published literature to appraise the prognostic value of lymphovascular invasion (LVI) in radical cystectomy specimens. Materials and Methods Following the PRISMA statement, PubMed, Cochrane Library, and SCOPUS database were searched from the respective dates of inception until June 2013. Results A total of 21 articles met the eligibility criteria for this systematic review, which included a total of 12,527 patients ranging from 57 to 4,257 per study. LVI was detected in 34.6% in radical cystectomy specimens. LVI was associated with higher pathological T stage and tumor grade, as well as lymph node metastasis. The pooled hazard ratio (HR) was statistically significant for recurrence-free survival (pooled HR, 1.61; 95% confidence interval [CI], 1.26–2.06), cancer-specific survival (pooled HR, 1.67; 95% CI, 1.38–2.01), and overall survival (pooled HR, 1.67; 95% CI, 1.38–2.01), despite the heterogeneity among included studies. On sensitivity analysis, the pooled HRs and 95% CIs were not significantly altered when any one study was omitted. The funnel plot for overall survival demonstrated a certain degree of asymmetry, which showed slight publication bias. Conclusions This meta-analysis indicates that LVI is significantly associated with poor outcome in patients with bladder cancer who underwent radical cystectomy. Adequately designed prospective studies are required to provide the precise prognostic significance of LVI in bladder cancer.
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Affiliation(s)
- Hwanik Kim
- Department of Urology, Seoul National University College of Medicine, Seoul, Korea
| | - Myong Kim
- Department of Urology, Seoul National University College of Medicine, Seoul, Korea
| | - Cheol Kwak
- Department of Urology, Seoul National University College of Medicine, Seoul, Korea
| | - Hyeon Hoe Kim
- Department of Urology, Seoul National University College of Medicine, Seoul, Korea
| | - Ja Hyeon Ku
- Department of Urology, Seoul National University College of Medicine, Seoul, Korea
- * E-mail:
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Gujam FJ, Going JJ, Edwards J, Mohammed ZM, McMillan DC. The role of lymphatic and blood vessel invasion in predicting survival and methods of detection in patients with primary operable breast cancer. Crit Rev Oncol Hematol 2014; 89:231-41. [DOI: 10.1016/j.critrevonc.2013.08.014] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2013] [Revised: 08/21/2013] [Accepted: 08/30/2013] [Indexed: 01/03/2023] Open
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Rezaianzadeh A, Talei A, Rajaeefard A, Hasanzadeh J, Tabatabai H, Tahmasebi S, Mousavizadeh A. Vascular invasion as an independent prognostic factor in lymph node negative invasive breast cancer. Asian Pac J Cancer Prev 2013; 13:5767-72. [PMID: 23317254 DOI: 10.7314/apjcp.2012.13.11.5767] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
INTRODUCTION Identification of simple and measurable prognostic factors is an important issue in treatment evaluation of breast cancer. The present study was conducted to evaluate the prognostic role of vascular invasion in lymph node negative breast cancer patients. METHODS in a retrospective design, we analyzed the recorded profiles of the 1,640 patients treated in the breast cancer department of Motahari clinic affiliated to Shiraz University of Medical Sciences, Shiraz, Iran, from January 1999 to December 2012. Overall and adjusted survivals were evaluated by the Cox proportional hazard model. All the hypotheses were considered two-sided and a p-value of 0.05 or less was considered as statistically significant. RESULTS Mean age in lymph node negative and positive patients was 50.0 and 49.8 respectively. In lymph node negative patients, the number of nodes, tumor size, lymphatic invasion, vascular invasion, progesterone receptor, and nuclear grade were significant predictors. In lymph node and lymphatic negative patients, vascular invasion also played a significant prognostic role in the survival which was not evident in lymph node negative patients with lymphatic invasion. DISCUSSION The results of our large cohort study, with long term follow up and using multivariate Cox proportional model and comparative design showed a significant prognostic role of vascular invasion in early breast cancer patients. Vascular invasion as an independent prognostic factor in lymph node negative invasive breast cancer.
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Affiliation(s)
- Abbas Rezaianzadeh
- Research Center for Health Sciences, Department of Epidemiology, School of Health and Nutrition, Shiraz University of Medical Sciences, shiraz, Iran
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Betterman KL, Paquet-Fifield S, Asselin-Labat ML, Visvader JE, Butler LM, Stacker SA, Achen MG, Harvey NL. Remodeling of the lymphatic vasculature during mouse mammary gland morphogenesis is mediated via epithelial-derived lymphangiogenic stimuli. THE AMERICAN JOURNAL OF PATHOLOGY 2012; 181:2225-38. [PMID: 23063660 DOI: 10.1016/j.ajpath.2012.08.035] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/16/2012] [Revised: 08/01/2012] [Accepted: 08/30/2012] [Indexed: 10/27/2022]
Abstract
Despite the key roles of lymphatic vessels in homeostasis and disease, the cellular sources of signals that direct lymphatic vascular growth and patterning remain unknown. Using high-resolution imaging in two and three dimensions, we demonstrated that postnatal mouse mammary gland lymphatic vessels share an intimate spatial association with epithelial ducts and large blood vessels. We further demonstrated that the lymphatic vasculature is remodeled together with the mammary epithelial tree and blood vasculature during postnatal mouse mammary gland morphogenesis. Neither estrogen receptor α nor progesterone receptor were detected in lymphatic endothelial cells in the mouse mammary gland, suggesting that mammary gland lymphangiogenesis is not likely regulated directly by these steroid hormones. Epithelial cells, especially myoepithelial cells, were determined to be a rich source of prolymphangiogenic stimuli including VEGF-C and VEGF-D with temporally regulated expression levels during mammary gland morphogenesis. Blockade of VEGFR-3 signaling using a small-molecule inhibitor inhibited the proliferation of primary lymphatic endothelial cells promoted by mammary gland conditioned medium, suggesting that lymphangiogenesis in the mammary gland is likely driven by myoepithelial-derived VEGF-C and/or VEGF-D. These findings provide new insight into the architecture of the lymphatic vasculature in the mouse mammary gland and, by uncovering the proximity of lymphatic vessels to the epithelial tree, suggest a potential mechanism by which metastatic tumor cells access the lymphatic vasculature.
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Affiliation(s)
- Kelly L Betterman
- Division of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia
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Yoshihara E, Smeets A, Laenen A, Reynders A, Soens J, Van Ongeval C, Moerman P, Paridaens R, Wildiers H, Neven P, Christiaens MR. Predictors of axillary lymph node metastases in early breast cancer and their applicability in clinical practice. Breast 2012; 22:357-61. [PMID: 23022046 DOI: 10.1016/j.breast.2012.09.003] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2012] [Revised: 08/31/2012] [Accepted: 09/07/2012] [Indexed: 11/26/2022] Open
Abstract
PURPOSE Lymph node involvement is the most important prognostic factor in breast cancer. It is a multifactorial event determined by patient and tumour characteristics. The purpose of this study was to determine clinical and pathological factors predictive for axillary lymph node metastasis (ALNM) in patients with early breast cancer and to build a model to portend lymph node involvement. METHODS We evaluated 1300 consecutive patients surgically treated in our institution (2007-2009) for cT1-T2 invasive breast cancer. The patient and tumour characteristics evaluated included: age at diagnosis, number of foci, histologic grade, location, tumour size, histologic subtype, lymphovascular invasion (LVI), estrogen-receptor (ER), progesterone-receptor (PR) and Her-2 status. Univariate and multivariate analyses were performed. Factors significantly associated with ALNM by univariate analysis plus histologic subtype were included in the multivariate analysis. RESULTS By univariate analysis, the incidence of ALNM was significantly associated with the presence of LVI (P < 0.0001), larger tumour size (P < 0.0001), higher histologic grade (P < 0.0001), retroareolar or lateral location in the breast (P < 0.0001), multiple foci (P = 0.0002) and in patients who underwent an axillary lymph node dissection. We found no effect of age, ER⁄PR nor HER-2 status. By multivariate analysis, ALNM was significantly associated with the presence of LVI (P < 0.0001), larger tumour size (P < 0.0001), axillary lymph node dissection (P = 0.0003), retroareolar and lateral tumour location in the breast (P = 0.0019) and the presence of multiple foci (P = 0.0155). CONCLUSIONS LVI and tumour size emerged as the most powerful independent predictors of ALNM, followed by the location of the tumour in the breast and the presence of multiple foci.
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Affiliation(s)
- Emi Yoshihara
- Multidisciplinary Breast Centre, University Hospitals Leuven, Herestraat 49, Leuven, Belgium
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Artacho-Cordón A, Artacho-Cordón F, Ríos-Arrabal S, Calvente I, Núñez MI. Tumor microenvironment and breast cancer progression: a complex scenario. Cancer Biol Ther 2012; 13:14-24. [PMID: 22336584 DOI: 10.4161/cbt.13.1.18869] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
It is now widely accepted that the development and progression of a tumor toward the malignant phenotype is highly dependent on interactions between tumor cells and the tumor microenvironment. Different components of the tumor microenvironment may have stimulatory or inhibitory effects on tumor progression by regulating the gene expression repertoire in tumor cells and stromal cells. This review analyzes novel research findings on breast cancer progression, discussing acquisition of the metastatic phenotype in breast disease in relation to different aspects of cross-talk among components of the tumor microenvironment. Knowledge of the interaction of all of these factors would contribute to elucidating the mechanisms that disrupt regulatory/signaling cascades and downstream effects in breast cancer.
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DNA copy number aberrations associated with lymphovascular invasion in upper urinary tract urothelial carcinoma. Cancer Genet 2012; 205:313-8. [PMID: 22749037 DOI: 10.1016/j.cancergen.2012.04.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2011] [Revised: 04/14/2012] [Accepted: 04/17/2012] [Indexed: 12/18/2022]
Abstract
Recent studies have reported that lymphovascular invasion (LVI) is a predictor of patient prognosis in upper urinary tract urothelial carcinoma (UUTUC). DNA copy number aberrations (DCNAs) identified by array-based comparative genomic hybridization (aCGH) had not previously been examined in UUTUC. We therefore examined DCNAs in UUTUC and compared them with DCNAs in LVI. We applied aCGH technology using DNA chips spotted with 4,030 BAC clones to 32 UUTUC patients. Frequent copy number gains were detected on chromosomal regions 8p23.1 and 20q13.12, whereas frequent copy number losses were detected on chromosomal regions 13q21.1, 17p13.1, 6q16.3, and 17p11.2. DCNAs occurred more frequently in tumors with LVI than in those without it (P = 0.0002), and this parameter was more closely associated with LVI than with the tumor grade or pT stage. Disease-specific survival rate was higher in tumors without LVI than in those with it (P = 0.0120); however, tumor grade and stage were not significant prognostic factors of patient outcome. These data support our hypothesis that tumors with LVI have more genetic alterations in terms of total numbers of DCNAs than those without, and provide proof that aggressive adjuvant therapy should be considered for UUTUC patients with LVI.
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Abstract
Historically, lymphatic vessels were considered passive participants in tumor metastasis by simply providing channels for tumor cells to transit to draining lymph nodes. The discovery of several key lymphatic-specific molecular markers and an increased availability of in vitro and in vivo experimental systems to study lymphatic biology have however highlighted a much more complex, active role for the lymphatic vasculature in metastatic tumor spread. This review will briefly describe the lymphatic system and lymphangiogenesis and then focus on the role of the lymphatic system in cancer metastasis. The progression of our understanding from the lymphatic system as a somewhat passive conduit for metastasis to an active participant in metastatic tumor dissemination, regulated by a complex array of lymphangiogenic factors, chemokines, and immune cell subsets, will be described.
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Affiliation(s)
- Ailsa Christiansen
- Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland
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Ran S, Montgomery KE. Macrophage-mediated lymphangiogenesis: the emerging role of macrophages as lymphatic endothelial progenitors. Cancers (Basel) 2012; 4:618-57. [PMID: 22946011 PMCID: PMC3430523 DOI: 10.3390/cancers4030618] [Citation(s) in RCA: 98] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
It is widely accepted that macrophages and other inflammatory cells support tumor progression and metastasis. During early stages of neoplastic development, tumor-infiltrating macrophages (TAMs) mount an immune response against transformed cells. Frequently, however, cancer cells escape the immune surveillance, an event that is accompanied by macrophage transition from an anti-tumor to a pro-tumorigenic type. The latter is characterized by high expression of factors that activate endothelial cells, suppress immune response, degrade extracellular matrix, and promote tumor growth. Cumulatively, these products of TAMs promote tumor expansion and growth of both blood and lymphatic vessels that facilitate metastatic spread. Breast cancers and other epithelial malignancies induce the formation of new lymphatic vessels (i.e., lymphangiogenesis) that leads to lymphatic and subsequently, to distant metastasis. Both experimental and clinical studies have shown that TAMs significantly promote tumor lymphangiogenesis through paracrine and cell autonomous modes. The paracrine effect consists of the expression of a variety of pro-lymphangiogenic factors that activate the preexisting lymphatic vessels. The evidence for cell-autonomous contribution is based on the observed tumor mobilization of macrophage-derived lymphatic endothelial cell progenitors (M-LECP) that integrate into lymphatic vessels prior to sprouting. This review will summarize the current knowledge of macrophage-dependent growth of new lymphatic vessels with specific emphasis on an emerging role of macrophages as lymphatic endothelial cell progenitors (M-LECP).
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Affiliation(s)
- Sophia Ran
- Author to whom correspondence should be addressed; E-Mail: ; Tel.: +1-217-545-7026; Fax: +1-217-545-7333
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Michikawa C, Uzawa N, Kayamori K, Sonoda I, Ohyama Y, Okada N, Yamaguchi A, Amagasa T. Clinical significance of lymphatic and blood vessel invasion in oral tongue squamous cell carcinomas. Oral Oncol 2011; 48:320-4. [PMID: 22178206 DOI: 10.1016/j.oraloncology.2011.11.014] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2011] [Revised: 11/14/2011] [Accepted: 11/20/2011] [Indexed: 02/07/2023]
Abstract
Although vascular invasion (VI) is recognized as an important predictor of lymph node metastasis and a significant prognostic factor in head and neck squamous cell carcinoma (HNSCC), there is currently no common definition for the pathological evaluation of VI status. We reviewed the medical records of 63 consecutive resected primary oral tongue SCCs (OTSCCs) without preoperative treatment between June 1999 and April 2008, and evaluated VI status by investigating lymphatic vessel invasion (LVI) and blood vessel invasion (BVI) by using immunohistochemistry (IHC) with monoclonal antibody D2-40 (D2-40) and Elastica van Gieson (EVG) staining, respectively. Subsequently, we analyzed their correlations with cervical lymph node metastasis and prognosis. LVI was found in 16 of the 63 tumors (25.4%) and BVI was in 32 tumors (50.8%). Univariate analysis revealed that the presence of LVI is statistically correlated with lymph node metastasis. Moreover, multivariate logistic regression analysis revealed that LVI is an independent risk factor of nodal metastasis (odds ratio=4.262, 95% confidence interval=1.262-14.397, p=0.020). In contrast, Kaplan-Meier survival analysis revealed that patients with BVI had a significantly shorter disease-free survival (DFS) and overall survival (OS) rates than those without BVI (68.6% versus 90.3%, p=0.028 and 68.6% versus 93.5%, p=0.013, respectively). The present study clearly demonstrated that LVI at primary OTSCC had significant correlation with lymph node metastasis, and that BVI was significantly associated with recurrence and poor prognosis. Evaluation of VI status, as LVI and BVI status separately, using IHC with D2-40 and EVG staining may be useful in predicting lymph node metastasis and poor prognosis in OTSCCs.
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Affiliation(s)
- Chieko Michikawa
- Maxillofacial Surgery, Maxillofacial Reconstruction and Function, Division of Maxillofacial and Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
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Song YJ, Shin SH, Cho JS, Park MH, Yoon JH, Jegal YJ. The role of lymphovascular invasion as a prognostic factor in patients with lymph node-positive operable invasive breast cancer. J Breast Cancer 2011; 14:198-203. [PMID: 22031801 PMCID: PMC3200515 DOI: 10.4048/jbc.2011.14.3.198] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2011] [Accepted: 08/12/2011] [Indexed: 11/30/2022] Open
Abstract
Purpose Lymphovascular invasion (LVI) is an important prognostic factor in patients with lymph node-negative patients with invasive breast cancer. However, the prognostic value of LVI it is unclear and controversial about its prognostic value in patients with lymph node-positive breast cancer patients. So, we report the an analysis of the prognostic significance of LVI in a large cohort study of patients with lymph node-positive patients with invasive breast cancer. Methods We retrospectively reviewed 967 patients with invasive breast cancer that had undergone surgical treatment at our hospital, from January 2004 to December 2007. Among these thempatients, 349 patients with lymph node-positive breast cancer patients are were included in this study. We evaluated clinical and pathological data in these patients, we compared with 5-year overall survival and disease-free survival between an LVI-present group and an LVI-absent group. Results The median follow-up was 48 months (range, 12-78 months), and the mean age of the patients was 48 years (range, 23-78 years). LVI was present in 192 patients (55%) of with tumors and was associated with age ≤40 years (p=0.009), high histologichistological grade (p=0.007), estrogen receptor status (p=0.001), tumor size ≥2 cm (p<0.001), and number of involved lymph nodes (p<0.001), but not with progesterone receptor status, HER2 status, p53 status, or tumor multiplicity. LVI was a significant independent prognostic factor for disease-free survival (p<0.001) and overall survival (p=0.006). By multivariate analysis revealed that LVI (p=0.003), number of involved lymph nodes (≥4; p=0.005), and high histological grade (II and III; p=0.02) was were an independent significant predictors of disease-free survival and overall survival in the whole group of patients. Conclusion In this case, we demonstrated that LVI is a significant predictor of poor prognosis in patients with lymph node-positive patients with primary invasive breast cancer, LVI is a significant predictive predictor value of poor prognosis. So, LVI should be considered in the therapeutic strategy as a decision making tool in the adjuvant chemotherapy setting.
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Affiliation(s)
- Young Ju Song
- Department of Surgery, Chonnam National University Medical School, Gwangju, Korea
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Patel SH, Kooby DA, Staley CA, Sarmiento JM, Maithel SK. The prognostic importance of lymphovascular invasion in cholangiocarcinoma above the cystic duct: a new selection criterion for adjuvant therapy? HPB (Oxford) 2011; 13:605-11. [PMID: 21843260 PMCID: PMC3183444 DOI: 10.1111/j.1477-2574.2011.00335.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2011] [Accepted: 05/07/2011] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Criteria for selecting patients to receive adjuvant chemotherapy in cases of resected intrahepatic or hilar cholangiocarcinoma (CC) are lacking. Some clinicians advocate the provision of adjuvant therapy in patients with lymph node (LN)-positive disease; however, nodal assessment is often inadequate. The aim of this study was to identify a surrogate criterion based on primary tumour characteristics. METHODS All patients who underwent resection for hilar or intrahepatic CC at a single institution between January 2000 and September 2009 were identified from a prospectively maintained database. Pathological factors were recorded. The primary outcome assessed was overall survival (OS). RESULTS In total, 69 patients underwent resection for hilar (n=34) or intrahepatic (n=35) CC. Their median age was 66 years and 27 patients (39%) were male. Median follow-up was 22 months and median OS was 17 months. Median tumour size was 5 cm. Overall, 23% of patients had a positive resection margin, 44% had perineural invasion, 32% had lymphovascular invasion (LVI) and 25% had positive LNs. The median number of LNs removed was two and the median number of positive LNs was zero. The presence of LVI was associated with reduced OS (11.9 months vs. 23.1 months; P=0.023). After accounting for all other adverse tumour factors, the presence of LVI persisted as the only negative prognostic factor for OS on multivariate Cox regression. CONCLUSIONS In patients who had undergone resection of hilar or intrahepatic CC, the presence of LVI was strongly associated with reduced OS. Thus the finding of LVI may potentially be used as a criterion in the selection of patients for adjuvant chemotherapy.
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Affiliation(s)
- Sameer H Patel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA
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Cornwell LB, Mcmasters KM, Chagpar AB. The Impact of Lymphovascular Invasion on Lymph Node Status in Patients with Breast Cancer. Am Surg 2011. [DOI: 10.1177/000313481107700722] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Lymphovascular invasion (LVI) is not uniformly found or reported in breast cancer tumor reports. We sought to determine the impact of the finding of LVI on various parameters of lymph node status in patients with breast cancer. A chart review was performed of 400 node-positive patients from a cohort of patients in a prospective multicenter national sentinel node registry. The finding of LVI was then correlated to number of positive sentinel nodes, the number of positive non-sentinel nodes, the lymph node ratio, and the size of the largest metastatic deposit. Of the 400 patients, data regarding LVI were missing in 98 (24.5%) cases. Although all of these patients were node-positive, LVI was noted to be present in 155 patients (38.8%) and absent in 147 (36.8%). LVI was found to correlate with more positive sentinel nodes (mean, 1.72 vs 1.35; P < 0.001), more positive nonsentinel nodes (mean, 2.16 vs 0.54; P < 0.001), and a higher lymph node ratio (0.29 vs 0.16; P < 0.001). LVI also correlated with size of largest metastatic deposit ( P = 0.002). Although LVI is known to be associated with lymph node status, it is not frequently noted on pathology reports. Given its prognostic value, LVI should be carefully evaluated and reported.
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Affiliation(s)
- Laura B. Cornwell
- Department of Surgery, University of Louisville, Louisville, Kentucky
| | | | - Anees B. Chagpar
- Department of Surgery, Yale University Schools of Medicine, New Haven, Connecticut
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Heerma van Voss MR, van der Groep P, Bart J, van der Wall E, van Diest PJ. Lympho-vascular invasion in BRCA related breast cancer compared to sporadic controls. BMC Cancer 2010; 10:145. [PMID: 20398395 PMCID: PMC2862041 DOI: 10.1186/1471-2407-10-145] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2009] [Accepted: 04/16/2010] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Germline mutations in the BRCA1 gene predispose to the development of breast cancer, exhibiting a specific histological phenotype. Identification of possible hallmarks of these tumors is important for selecting patients for genetic screening and provides inside in carcinogenetic pathways.Since BRCA1-associated breast cancers have pushing borders that prevent them from easily reaching vessels and are often of the medullary (like) type that is known to have a low rate of lympho-vascular invasion (LVI), we hypothesized that absence of LVI could characterize BRCA1 related breast cancer. METHODS A population of 68 BRCA1 related invasive breast cancers was evaluated for LVI by an experienced breast pathologist blinded to mutation status, and compared to a control group matched for age, grade and tumor type. RESULTS LVI was present in 25.0% of BRCA1 related cases, compared to 20.6% of controls (P = 0.54, OR = 1.29, CI 0.58-2.78). CONCLUSION LVI is frequent in BRCA1 germline mutation related breast cancers, but seems to occur as often in sporadic controls matched for age, grade and tumor type. Apparently, these hereditary cancers find their way to the blood and lymph vessels despite their well demarcation and often medullary differentiation.
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Kim DS, Lee YH, Cho KS, Cho NH, Chung BH, Hong SJ. Lymphovascular invasion and pT stage are prognostic factors in patients treated with radical nephroureterectomy for localized upper urinary tract transitional cell carcinoma. Urology 2010; 75:328-32. [PMID: 20018349 DOI: 10.1016/j.urology.2009.07.1350] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2009] [Revised: 07/08/2009] [Accepted: 07/12/2009] [Indexed: 10/20/2022]
Abstract
OBJECTIVES To investigate the prognostic significance of lymphovascular invasion (LVI) in patients with localized upper urinary tract transitional cell carcinoma (UUT-TCC) after radical nephroureterectomy. METHODS The clinical records of 271 patients with UUT-TCC who underwent radical nephroureterectomy between 1986 and 2006 were reviewed. Patients with pT4 stage, lymph node involvement, or distant metastasis were excluded. A total of 238 patients with pTa-3N0M0 were eligible. The prognostic significance of various clinicopathologic factors was analyzed using univariate and multivariate analysis. The mean age was 64.1 years (range, 25-91 years) and the median follow-up duration was 53.4 months (range, 3-240 months). RESULTS LVI was present in 31 patients (13%). LVI was related to higher pT stage, high tumor grade, sessile architecture, and squamous differentiation. On univariate analysis, tumor architecture, squamous differentiation, LVI, tumor grade, and pT stage influenced disease-specific survival. On multivariate analysis, LVI (hazards ratio [HR], 2.33; P = .014) and pT stage (HR, 2.07; P = .021) showed significantly different rates of disease-specific survival. Patients were classified according to pT stage and LVI. The high-risk group (pT3 and LVI+) showed significantly worse disease-specific survival than the low- (pT < or = 2 and LVI-) or intermediate-risk groups (pT3 and LVI-, pT < or = 2 and LVI+) (P <.001 and P = .032, respectively). CONCLUSIONS LVI and pT stage are significant prognostic factors for recurrence-free and cancer-specific survivals in patients with localized UUT-TCC. LVI and pT stage would be helpful for selecting patients who are appropriate for postoperative adjuvant chemotherapy.
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Affiliation(s)
- Dong Suk Kim
- Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea
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The Implications of the Imaging Manifestations of Multifocal and Diffuse Breast Cancers. Breast Cancer 2010. [DOI: 10.1007/978-1-84996-314-5_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Ran S, Volk L, Hall K, Flister MJ. Lymphangiogenesis and lymphatic metastasis in breast cancer. ACTA ACUST UNITED AC 2009; 17:229-51. [PMID: 20036110 DOI: 10.1016/j.pathophys.2009.11.003] [Citation(s) in RCA: 181] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2009] [Revised: 04/11/2009] [Accepted: 10/23/2009] [Indexed: 01/03/2023]
Abstract
Lymphatic metastasis is the main prognostic factor for survival of patients with breast cancer and other epithelial malignancies. Mounting clinical and experimental data suggest that migration of tumor cells into the lymph nodes is greatly facilitated by lymphangiogenesis, a process that generates new lymphatic vessels from pre-existing lymphatics with the aid of circulating lymphatic endothelial progenitor cells. The key protein that induces lymphangiogenesis is vascular endothelial growth factor receptor-3 (VEGFR-3), which is activated by vascular endothelial growth factor-C and -D (VEGF-C and VEGF-D). These lymphangiogenic factors are commonly expressed in malignant, tumor-infiltrating and stromal cells, creating a favorable environment for generation of new lymphatic vessels. Clinical evidence demonstrates that increased lymphatic vessel density in and around tumors is associated with lymphatic metastasis and reduced patient survival. Recent evidence shows that breast cancers induce remodeling of the local lymphatic vessels and the regional lymphatic network in the sentinel and distal lymph nodes. These changes include an increase in number and diameter of tumor-draining lymphatic vessels. Consequently, lymph flow away from the tumor is increased, which significantly increases tumor cell metastasis to draining lymph nodes and may contribute to systemic spread. Collectively, recent advances in the biology of tumor-induced lymphangiogenesis suggest that chemical inhibitors of this process may be an attractive target for inhibiting tumor metastasis and cancer-related death. Nevertheless, this is a relatively new field of study and much remains to be established before the concept of tumor-induced lymphangiogenesis is accepted as a viable anti-metastatic target. This review summarizes the current concepts related to breast cancer lymphangiogenesis and lymphatic metastasis while highlighting controversies and unanswered questions.
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Affiliation(s)
- Sophia Ran
- Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, 801 N. Rutledge, Springfield, IL 62794-9678, USA
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Li H, Feng L, Xu Y, Yao L, Ouyang T, Li J, Wang T, Fan Z, Lin B, Li J, Xie Y. The association of CYP2D6 *10 polymorphism with breast cancer risk and clinico-pathologic characteristics in Chinese women. Acta Oncol 2009; 45:597-601. [PMID: 16864175 DOI: 10.1080/02841860600660803] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
A relatively little is known of whether CYP2D6 *10 (188 C to T) polymorphism mediates susceptibility to breast cancer. In this study the CYP2D6 *10 polymorphism was detected in Chinese women (286 breast cancer patients and 305 healthy women) by a PCR-RFLP assay. We found that women with the 188T/T genotype displayed a slightly increased risk for breast cancer as compared with those with the 188C/C genotype (OR 1.36, CI 0.89-2.1), the association of the 188T/T genotype with breast cancer risk was more pronounced among postmenopausal women (OR 1.49, CI 0.8-2.76), but the association did not reach statistical significance. Furthermore, we found that patients carrying the 188T/T or T/C genotype were more likely to be a positive lymph node status than those with the 188C/C genotype (OR 2.12, CI 1.08-4.18, P = 0.019). Our results suggest that CYP2D6 *10 mutant 188T/T genotype displays a non-significant increased risk for breast cancer. Moreover, patients carrying 188T/T or T/C genotype might exhibit a more aggressive phenotype than those carrying 188C/C genotype, as the observation association of genotype with clinical outcome may be due to chance, therefore, further studies are required to confirm our present findings.
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Affiliation(s)
- Hongxia Li
- Breast Centre, Beijing Cancer Hospital, Peking University School of Oncology, Beijing, PR China
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Raynor MP, Stephenson SA, Pittman KB, Walsh DCA, Henderson MA, Dobrovic A. Identification of circulating tumour cells in early stage breast cancer patients using multi marker immunobead RT-PCR. J Hematol Oncol 2009; 2:24. [PMID: 19500345 PMCID: PMC2712470 DOI: 10.1186/1756-8722-2-24] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2009] [Accepted: 06/05/2009] [Indexed: 11/20/2022] Open
Abstract
Introduction The ability to screen blood of early stage operable breast cancer patients for circulating tumour cells is of potential importance for identifying patients at risk of developing distant relapse. We present the results of a study of the efficacy of the immunobead RT-PCR method in identifying patients with circulating tumour cells. Results Immunomagnetic enrichment of circulating tumour cells followed by RT-PCR (immunobead RT-PCR) with a panel of five epithelial specific markers (ELF3, EPHB4, EGFR, MGB1 and TACSTD1) was used to screen for circulating tumour cells in the peripheral blood of 56 breast cancer patients. Twenty patients were positive for two or more RT-PCR markers, including seven patients who were node negative by conventional techniques. Significant increases in the frequency of marker positivity was seen in lymph node positive patients, in patients with high grade tumours and in patients with lymphovascular invasion. A strong trend towards improved disease free survival was seen for marker negative patients although it did not reach significance (p = 0.08). Conclusion Multi-marker immunobead RT-PCR analysis of peripheral blood is a robust assay that is capable of detecting circulating tumour cells in early stage breast cancer patients.
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Affiliation(s)
- Michael P Raynor
- Department of Haematology/Oncology, The Queen Elizabeth Hospital, Adelaide, South Australia 5011, Australia.
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Tot T. The metastatic capacity of multifocal breast carcinomas: extensive tumors versus tumors of limited extent. Hum Pathol 2009; 40:199-205. [DOI: 10.1016/j.humpath.2008.07.001] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2008] [Revised: 06/27/2008] [Accepted: 07/07/2008] [Indexed: 11/28/2022]
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The impact of lymphovascular invasion on survival in oral carcinoma. Oral Oncol 2009; 45:10-5. [DOI: 10.1016/j.oraloncology.2008.03.009] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2008] [Revised: 03/07/2008] [Accepted: 03/11/2008] [Indexed: 11/23/2022]
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Budrukkar AN, Sarin R, Chinoy RF, Badwe R, Shrivastava SK, Dinshaw KA. Prognostic factors in node negative premenopausal women treated with breast conserving therapy without adjuvant systemic therapy. Breast 2008; 17:263-9. [DOI: 10.1016/j.breast.2007.10.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2007] [Revised: 09/10/2007] [Accepted: 10/12/2007] [Indexed: 11/26/2022] Open
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Akao J, Matsuyama H, Yamamoto Y, Hara T, Kawai Y, Sakano S, Ohmi C, Gondo T, Naito K. Clinical significance of lymphovascular invasion in upper urinary tract urothelial cancer. BJU Int 2008; 102:572-5. [PMID: 18485032 DOI: 10.1111/j.1464-410x.2008.07749.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
OBJECTIVES To clarify the significance of lymphovascular invasion (LVI) in patients with pT3N0M0 upper urinary tract (UUT) urothelial carcinoma (UC) relative to prognosis in terms of disease-specific survival, as LVI, which implies both blood vessel and lymph vessel involvement, is reportedly a poor prognostic factor in patients with UUT-UC. PATIENTS AND METHODS The clinical records of 90 patients who had surgery for UUT-UC were reviewed retrospectively. The median patient age was 71 years and the median follow-up was 42 months. The prognostic significances of LVI (with vs without), T stage (< 1 vs 2-4), grade (1-2 vs 3), N stage (0 vs 1-2), age (< or = 70 vs > 70 years), gender and tumour location (renal pelvis vs ureter) for survival time were evaluated. RESULTS LVI of UUT-UC was found in 34 patients (37.8%). There were significantly higher frequencies of LVI with advancing stage and lymph node metastasis. Kaplan-Meier analysis showed that LVI was strongly associated with disease-specific survival in all patients (P < 0.001) and in patients with pT3N0M0 disease (P < 0.001). Univariate analyses showed that LVI, T stage, N stage and tumour grade were significantly related to disease-specific survival in all patients (P < 0.001, < 0.001, 0.003 and 0.007, respectively). Multivariate analysis using Cox proportional hazards model showed that LVI was the only prognostic factor with independent significance for disease-specific survival (P < 0.001). CONCLUSIONS LVI appears to be an important and independent prognostic factor for UUT-UC in patients treated by nephroureterectomy. Our data suggest that the LVI status might be a predictive marker for disease-specific survival in patients with T3N0M0 UTT-UC.
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Affiliation(s)
- Jumpei Akao
- Department of Urology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
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Improved methods of detection of lymphovascular invasion demonstrate that it is the predominant method of vascular invasion in breast cancer and has important clinical consequences. Am J Surg Pathol 2008; 31:1825-33. [PMID: 18043036 DOI: 10.1097/pas.0b013e31806841f6] [Citation(s) in RCA: 141] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The presence of vascular invasion (VI), encompassing both lymphovascular invasion (LVI) and blood vascular invasion (BVI), in breast cancer has been found to be a poor prognostic factor. It is not clear, however, which type of VI plays the major role in metastasis. The aims of this study were to use an endothelial subtype specific immunohistochemical approach to distinguish between LVI and BVI by comparing the differential expression of blood vascular (CD34 and CD31) and lymphatic markers (podoplanin/D2-40) to determine their prognostic role in a well-characterized group of breast cancer patients with known long-term follow-up. Sections from 177 consecutive paraffin-embedded archival specimens of primary invasive breast cancer were stained for expression of podoplanin, D2-40, CD31, and CD34. BVI and LVI were identified and results were correlated with clinicopathologic criteria and patient survival. VI was detected in 56/177 specimens (31.6%); 54 (96.4%) were LVI and 2 (3.5%) were BVI. The presence of LVI was significantly associated with the presence of lymph node metastasis, larger tumor size, development of distant metastasis, regional recurrence and worse disease-free interval and overall survival. In multivariate analysis, LVI retained significance association with decreased disease-free interval and overall survival. In conclusion, VI in breast cancer is predominantly of lymph vessels and is a powerful independent prognostic factor, which is associated with risk of recurrence and death from the disease. The use of immunohistochemical staining with a lymphendothelial specific marker such as podoplanin/D2-40 increases the accuracy of identification of patients with tumor associated LVI.
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Whitehurst B, Flister MJ, Bagaitkar J, Volk L, Bivens CM, Pickett B, Castro-Rivera E, Brekken RA, Gerard RD, Ran S. Anti-VEGF-A therapy reduces lymphatic vessel density and expression of VEGFR-3 in an orthotopic breast tumor model. Int J Cancer 2007; 121:2181-91. [PMID: 17597103 DOI: 10.1002/ijc.22937] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Because metastasis contributes significantly to cancer mortality, understanding its mechanisms is crucial to developing effective therapy. Metastasis is facilitated by lymphangiogenesis, the growth of new intratumoral or peritumoral lymphatic vessels from pre-existing vessels. Vascular endothelial growth factor A (VEGF-A) is a well-known angiogenic factor. Increasing evidence implicates VEGF-A in lymphangiogenesis, although the mechanism of its pro-lymphangiogenic effect is poorly understood. We examined the effect of the anti-VEGF-A neutralizing antibody 2C3 on tumor lymphangiogenesis and metastasis in an orthotopic breast carcinoma model using MDA-MB-231 cells and its luciferase-tagged derivative, 231-Luc(+) cells. Anti-VEGF-A antibody therapy reduced blood and lymphatic vessel densities by 70% and 80%, respectively, compared with the control antibody. Treatment with 2C3 antibody also decreased incidence of lymphatic and pulmonary metastases by 3.2- and 4.5-fold, respectively. Macrophage infiltration was reduced in 2C3-treated tumors by 32%, but VEGF-C expression was unchanged. In contrast, neoplastic cells and blood vessels in tumors from 2C3-treated mice expressed significantly less angiopoietin-2 (Ang-2) than tumors from control mice. The reduction in Ang-2 was associated with inhibition of VEGFR-3 expression in intratumoral lymphatic endothelial cells. Both VEGF-A and Ang-2 upregulated the expression of VEGFR-3 in cultured lymphatic endothelial cells. VEGF-A induced proliferation of lymphatic endothelial cells was reduced by 50% by soluble Tie-2, suggesting that Ang-2 is an intermediary of the pro-lymphangiogenic VEGF-A effect. These results suggest a novel mechanism by which anti-VEGF-A therapy may suppress tumor lymphangiogenesis and subsequent metastasis supporting the use of anti-VEGF-A therapy to control metastasis clinically.
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Affiliation(s)
- Brandt Whitehurst
- Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA
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Kiruparan P, Forrest L. Prediction in breast cancer of the extent of axillary node involvement from the size and lymphovascular invasion status of the primary tumour: Medico-legal considerations. Eur J Surg Oncol 2007; 33:435-7. [PMID: 17137746 DOI: 10.1016/j.ejso.2006.10.031] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2006] [Accepted: 10/20/2006] [Indexed: 11/22/2022] Open
Abstract
AIM To ascertain for medico-legal purposes in the United Kingdom, the extent to which in breast cancer primary tumour size and lympho-vascular invasion (LVI) status determine axillary node staging. METHODS Four hundred and fifty symptomatic patients had their tumour sizes stratified into 1cm ranges and the percentage incidence/probability of the axillary stage being 1, 2 or 3 was calculated separately for those tumours that showed no evidence of LVI and those that did. RESULTS The presence of LVI has a marked effect on the likelihood and extent of axillary node involvement for all primary tumour sizes. CONCLUSIONS This needs to be recognized and quantified when prediction of this extent is made for medico-legal purposes. Within the constraints of the 'balance of probabilities' argument in UK law, it is rarely possible to differentiate between the likelihood of the axillary stage being 2 or 3.
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Affiliation(s)
- P Kiruparan
- Department of Surgery, Breast Care Unit, Victoria Hospital NHS Trust, Whinney Heys Road, Blackpool, Lancashire, FY3 8NR, UK
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Alexander BM, Bryan B, Collins LC, Recht A. Atypical Cytology in a Persistent Seroma Following Mastectomy for Breast Cancer: A Case Report and Review of the Literature. Breast J 2007; 13:196-9. [PMID: 17319864 DOI: 10.1111/j.1524-4741.2007.00399.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Improvement in local control with radiation therapy translates to a survival benefit in patients with breast cancer. The magnitude this benefit is proportional to the magnitude of the improvement in local control. Since the proportional reduction of local recurrence with the addition of radiation is relatively constant, it is important to determine the probability of local recurrence in order to guide therapy. There are a number of factors, including lymph node involvement, lymphovascular invasion, and size of the primary tumor that correlate with risk of local recurrence. There is very little data on the prognostic significance of malignant cells in seroma fluid after mastectomy or axillary dissection. We report a case of a woman with atypical cells in a persistent seroma following mastectomy for node negative infiltrating ductal carcinoma.
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Affiliation(s)
- Brian M Alexander
- Harvard Radiation Oncology Program, Boston, Massachusetts 02115, USA.
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Neri A, Marrelli D, Rossi S, De Stefano A, Mariani F, De Marco G, Caruso S, Corso G, Cioppa T, Pinto E, Roviello F. Breast cancer local recurrence: risk factors and prognostic relevance of early time to recurrence. World J Surg 2007; 31:36-45. [PMID: 17180474 DOI: 10.1007/s00268-006-0097-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Local recurrence occurs in 10%-20% of patients treated with breast-conserving surgery for stage I-II breast cancer. The aim of the present study was to investigate breast cancer local recurrence, potential risk factors, and prognostic impact. METHODS A total of 503 patients treated with breast-conserving surgery were included in the study. All patients underwent axillary dissection and postoperative radiotherapy, and all patients had negative margins at pathological examination. Median follow-up was 82 months. Local recurrence was classified as early when it occurred within 2 years from surgery. The risk factors for local recurrence and overall survival were estimated by univariate and multivariate analyses. RESULTS Forty-six cases (9.1%) of local recurrence were observed, 11 of which occurred within 24 months of surgery; the other 35, sometime later. Statistically significant risk factors for local recurrence were premenopausal status, peritumoral vascular invasion, multifocality, and absence of estrogen receptors. Independent negative prognostic factors for overall survival at 5 and 10 years were N stage, absence of estrogen receptors, and early time to recurrence. Overall survival at 10 years was 10.0% for patients with early recurrence, 87.5% for patients with late recurrence, and 87.9% for patients without recurrence. CONCLUSIONS None of the studied clinicopathological characteristics alone is a determinant for the choice of surgical treatment. Younger patients treated with breast-conserving surgery should receive aggressive postsurgical treatment and should be followed with an intensive follow-up program when metastatic axillary lymph nodes, negative estrogen receptors, or peritumoral vascular invasion are present.
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Affiliation(s)
- A Neri
- Dipartimento di Patologia Generale ed Umana, Sezione di Chirurgia Oncologica, Università degli Studi di Siena, Viale Bracci 1, 53100 Siena, Italy.
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Clinical relevance of the distribution of the lesions in 500 consecutive breast cancer cases documented in large-format histologic sections. Cancer 2007; 110:2551-60. [DOI: 10.1002/cncr.23052] [Citation(s) in RCA: 89] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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