|
1
|
Caramaschi S, Mangogna A, Bertoni L, Manfredini M, Farnetani F, Parente P, Attino V, Cazzato G, Salviato T, Pellacani G, Reggiani Bonetti L. High charge of cerebroid nests in nodular melanomas predicts tumor aggressiveness and high mutational tumoral burden: a pilot study. Front Oncol 2024; 14:1336895. [PMID: 39099686 PMCID: PMC11294109 DOI: 10.3389/fonc.2024.1336895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Accepted: 07/02/2024] [Indexed: 08/06/2024] Open
Abstract
Purpose Even today, melanoma is a highly aggressive neoplasm with a high mortality rate. The nodular type is very aggressive and has cerebroid nests of melanocytes (CNMs) at the growth edge, morphologically similar to the poorly differentiated neoplastic epithelial cell clusters described in colorectal, breast, and endometrioid endometrial cancers. Patients and methods We selected 25 nodular melanomas (NMs) with known molecular profiles, of which the entire paraffin-embedded lesion was available. We counted CNMs under a microscopic at a magnification of 20x (i.e., a microscopic field with a major axis of 1 mm). Based on the number of CNMs in the area, melanomas were classified into three groups: G1 (CNMs ranging from 0 to 4), G2 (CNMs ranging from 5 to 9), and G3 (CNMs ≥ 10). The presence of CNMs and their counts were compared with molecular and histopathological data. Results Seventeen (NMs) were grouped as G1 (68%), 5 as G2 (20%), and 3 as G3 (12%) based on CNMs count. The presence of CNMs correlated with epithelioid cell morphology (p < 0.05), Clark IV and V levels (p < 0.05), vascular invasion (p < 0.05), and biological mutants (p < 0.05). Melanomas with ≥ 10 CNMs more frequently show ulceration (p < 0.02) and the BRAF V600E mutation (p < 0.02). Conclusion CNMs count has a predictive role regardless of tumor size; their association with the BRAF V600E mutation suggests their predictive significance in response to biologics. However, further investigations are needed to strengthen this hypothesis.
Collapse
Affiliation(s)
- Stefania Caramaschi
- Clinical and Experimental Medicine PhD Program, Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
- Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Alessandro Mangogna
- Institute of Pathologic Anatomy, Department of Medicine, University of Udine, Udine, Italy
| | - Laura Bertoni
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Marco Manfredini
- Dermatology Unit, Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Francesca Farnetani
- Dermatology Unit, Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Paola Parente
- Unit of Pathology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
| | - Vito Attino
- Unit of Pathology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
| | - Gerardo Cazzato
- Section of Molecular Pathology, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, Bari, Italy
| | | | - Giovanni Pellacani
- Dermatology Clinic, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Roma, Italy
| | - Luca Reggiani Bonetti
- Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy
- Pathology Unit, University Hospital of Modena, Modena, Italy
| |
Collapse
|
|
2
|
Wang J, Zhang X, Gan T, Rao NN, Deng K, Yang JL. Risk factors and a predictive nomogram for lymph node metastasis in superficial esophageal squamous cell carcinoma. World J Gastroenterol 2023; 29:6138-6147. [PMID: 38186680 PMCID: PMC10768412 DOI: 10.3748/wjg.v29.i47.6138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Revised: 11/07/2023] [Accepted: 12/08/2023] [Indexed: 12/19/2023] Open
Abstract
BACKGROUND Superficial esophageal squamous cell carcinoma (ESCC) is defined as cancer infiltrating the mucosa and submucosa, regardless of regional lymph node metastasis (LNM). Endoscopic resection of superficial ESCC is suitable for lesions that have no or low risk of LNM. Patients with a high risk of LNM always need further treatment after endoscopic resection. Therefore, accurately assessing the risk of LNM is critical for additional treatment options. AIM To analyze risk factors for LNM and develop a nomogram to predict LNM risk in superficial ESCC patients. METHODS Clinical and pathological data of superficial ESCC patients undergoing esophagectomy from January 1, 2009 to January 31, 2016 were collected. Logistic regression analysis was used to predict LNM risk factors, and a nomogram was developed based on risk factors derived from multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to obtain the accuracy of the nomogram model. RESULTS A total of 4660 patients with esophageal cancer underwent esophagectomy. Of these, 474 superficial ESCC patients were enrolled in the final analysis, with 322 patients in the training set and 142 patients in the validation set. The prevalence of LNM was 3.29% (5/152) for intramucosal cancer and increased to 26.40% (85/322) for submucosal cancer. Multivariate logistic analysis showed that tumor size, invasive depth, tumor differentiation, infiltrative growth pattern, tumor budding, and lymphovascular invasion were significantly correlated with LNM. A nomogram using these six variables showed good discrimination with an area under the ROC curve of 0.789 (95%CI: 0.737-0.841) in the training set and 0.827 (95%CI: 0.755-0.899) in the validation set. CONCLUSION We developed a useful nomogram model to predict LNM risk for superficial ESCC patients which will facilitate additional decision-making in treating patients who undergo endoscopic resection.
Collapse
Affiliation(s)
- Jin Wang
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xian Zhang
- Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Tao Gan
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ni-Ni Rao
- School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610064, Sichuan Province, China
| | - Kai Deng
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jin-Lin Yang
- Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| |
Collapse
|
|
3
|
Saez de Gordoa K, Rodrigo-Calvo MT, Archilla I, Lopez-Prades S, Diaz A, Tarragona J, Machado I, Ruiz Martín J, Zaffalon D, Daca-Alvarez M, Pellisé M, Camps J, Cuatrecasas M. Lymph Node Molecular Analysis with OSNA Enables the Identification of pT1 CRC Patients at Risk of Recurrence: A Multicentre Study. Cancers (Basel) 2023; 15:5481. [PMID: 38001742 PMCID: PMC10670609 DOI: 10.3390/cancers15225481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 11/11/2023] [Accepted: 11/14/2023] [Indexed: 11/26/2023] Open
Abstract
Early-stage colorectal carcinoma (CRC)-pT1-is a therapeutic challenge and presents some histological features related to lymph node metastasis (LNM). A significant proportion of pT1 CRCs are treated surgically, resulting in a non-negligible surgical-associated mortality rate of 1.5-2%. Among these cases, approximately 6-16% exhibit LNM, but the impact on survival is unclear. Therefore, there is an unmet need to establish an objective and reliable lymph node (LN) staging method to optimise the therapeutic management of pT1 CRC patients and to avoid overtreating or undertreating them. In this multicentre study, 89 patients with pT1 CRC were included. All histological features associated with LNM were evaluated. LNs were assessed using two methods, One-Step Nucleic Acid Amplification (OSNA) and the conventional FFPE plus haematoxylin and eosin (H&E) staining. OSNA is an RT-PCR-based method for amplifying CK19 mRNA. Our aim was to assess the performance of OSNA and H&E in evaluating LNs to identify patients at risk of recurrence and to optimise their clinical management. We observed an 80.9% concordance in LN assessment using the two methods. In 9% of cases, LNs were found to be positive using H&E, and in 24.7% of cases, LNs were found to be positive using OSNA. The OSNA results are provided as the total tumour load (TTL), defined as the total tumour burden present in all the LNs of a surgical specimen. In CRC, a TTL ≥ 6000 CK19 m-RNA copies/µL is associated with poor prognosis. Three patients had TTL > 6000 copies/μL, which was associated with higher tumour budding. The discrepancies observed between the OSNA and H&E results were mostly attributed to tumour allocation bias. We concluded that LN assessment with OSNA enables the identification of pT1 CRC patients at some risk of recurrence and helps to optimise their clinical management.
Collapse
Affiliation(s)
- Karmele Saez de Gordoa
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
| | - Maria Teresa Rodrigo-Calvo
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
| | - Ivan Archilla
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
| | - Sandra Lopez-Prades
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
| | - Alba Diaz
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Department of Clinical Foundations, University of Barcelona (UB), 08036 Barcelona, Spain
| | - Jordi Tarragona
- Pathology Department, Hospital Arnau de Vilanova, 25198 Lleida, Spain;
| | - Isidro Machado
- Pathology Department, Instituto Valenciano de Oncología, Hospital Quirón-Salud Valencia, University of Valencia, 46010 Valencia, Spain;
- Centro de Investigación Biomédica en Red en Cancer (CIBERONC), 28029 Madrid, Spain
| | - Juan Ruiz Martín
- Pathology Department, Virgen de la Salud Hospital, 45071 Toledo, Spain;
| | - Diana Zaffalon
- Gastroenterology Department, Consorci Sanitari de Terrassa, 08227 Terrassa, Spain;
| | - Maria Daca-Alvarez
- Gastroenterology Department, Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain;
| | - Maria Pellisé
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Gastroenterology Department, Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain;
| | - Jordi Camps
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Cell Biology and Medical Genetics Unit, Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, Autonomous University of Barcelona (UAB), 08193 Bellaterra, Spain
| | - Miriam Cuatrecasas
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Department of Clinical Foundations, University of Barcelona (UB), 08036 Barcelona, Spain
| |
Collapse
|
|
4
|
Tang CT, Li J, Wang P, Chen YX, Zeng CY. Prediction model for lymph node metastasis in superficial colorectal cancer: a better choice than computed tomography. Surg Endosc 2023; 37:7444-7454. [PMID: 37400690 DOI: 10.1007/s00464-023-10222-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 06/16/2023] [Indexed: 07/05/2023]
Abstract
BACKGROUND Risk evaluation of lymph node metastasis (LNM) in superficial colorectal cancer resected by endoscopic surgery is critical for determining subsequent therapeutic strategies, but the role of existing clinical methods, including computed tomography, remains limited. METHODS Features of the nomogram were determined by logistic regression analysis, and the performance was validated by calibration plots, ROC curves and DCA curves in both the training set and the validation set. RESULTS A total of 608 consecutive superficial CRC cases were randomly divided into 426 training and 182 validation cases. Univariate and multivariate logistic regression analyses revealed that age < 50, tumour budding, lymphatic invasion and lower HDL levels were risk factors for LNM. Stepwise regression and the Hosmer‒Lemeshow goodness of fit test showed that the nomogram had good performance and discrimination, which was validated by ROC curves and calibration plots. Internal and external validation demonstrated that the nomogram had a higher C-index (training group, 0.749, validation group, 0.693). DCA and clinical impact curves graphically show that the use of the nomogram to predict LNM had remarkable predictive power. Finally, in comparison with CT diagnosis, the nomogram also visually showed higher superiority, as demonstrated by ROC, DCA and clinical impact curves. CONCLUSION Using common clinicopathologic factors, a noninvasive nomogram for individualized prediction of LNM after endoscopic surgery was conveniently established. Nomograms have great superiority in the risk stratification of LNM compared with traditional CT imaging.
Collapse
Affiliation(s)
- Chao-Tao Tang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
| | - Jun Li
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
| | - Peng Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
| | - You-Xiang Chen
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
| | - Chun-Yan Zeng
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China.
| |
Collapse
|
|
5
|
Tunuguntla A, Suresh T, PN S. Association Between the Immunohistochemistry Expression of E-cadherin, Beta-Catenin, and CD44 in Colorectal Adenocarcinoma. Cureus 2023; 15:e35686. [PMID: 37012965 PMCID: PMC10066707 DOI: 10.7759/cureus.35686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/02/2023] [Indexed: 03/06/2023] Open
Abstract
Background Colorectal cancer is a leading cause of cancer-related deaths worldwide, and epithelial-mesenchymal transition (EMT) plays an important role in cancer metastasis. In EMT, there is downregulation of E-cadherin, an intracellular adhesion molecule, as well as mutations in beta-catenin genes. On immunohistochemistry (IHC), the expression of CD44 portrays stem cell differentiation, which, in turn, is strongly associated with EMT. Thus, newer targeted therapies can be advised based on the expression of EMT and stem cell differentiation. Aims and objectives To determine the IHC expression of E-cadherin, beta-catenin, and CD44 in colorectal adenocarcinoma and find the association of the IHC expression of E-cadherin, beta-catenin, and CD44 with the histopathological grade, stage, lymph node metastasis, and lymphovascular invasion of colorectal adenocarcinoma. Materials and methods Fifty histologically proven cases of colorectal adenocarcinoma from 2016 to 2021 were included in this study, and clinicopathological data including age, gender, grading, TNM (tumour, node, and metastasis) staging, and lymph node metastasis were collected and hematoxylin and eosin slides were reviewed. IHC staining for E-cadherin, beta-catenin, and CD44 was done for all cases using the peroxidase and anti-peroxidase method, and the results were analysed. Results Peak incidence occurred in the 61-70 years age group (36%), and the most common site of the tumour was the rectal area (48%). The majority of the cases were in TNM stage II (37.3%), and a low expression of E-cadherin was found to be associated with higher T stage (p = 0.03), TNM staging (p = 0.04), as well as the presence of lymph node metastasis (p = 0.006). High beta-catenin expression was observed to have a significant correlation with a higher T stage (p = 0.006) and TNM staging (p = 0.005), while high CD44 expression was found to be associated with lymph node metastasis (p = 0.01). Altered expression of EMT-related proteins (E-cadherin and beta-catenin) showed a significant correlation with higher T stage (p = 0.03), TNM staging (p = 0.016), and lymph node metastasis (0.04). Conclusions EMT and cancer stem cell IHC markers are biomarkers for aggressive tumour growth and lymph node metastasis. Hence, EMT markers (E-cadherin and beta-catenin) and cancer stem cell markers (CD44) can be used as prognostic markers.
Collapse
|
|
6
|
Rodrigo-Calvo MT, Saez de Gordoa K, Lopez-Prades S, Archilla I, Diaz A, Berrios M, Camps J, Musulen E, Cuatrecasas M. Tumour Cell Seeding to Lymph Nodes from In Situ Colorectal Cancer. Cancers (Basel) 2023; 15:cancers15030842. [PMID: 36765800 PMCID: PMC9913321 DOI: 10.3390/cancers15030842] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 01/25/2023] [Accepted: 01/27/2023] [Indexed: 02/01/2023] Open
Abstract
Lymph node (LN) metastasis is an important prognostic factor in colorectal cancer (CRC). We aimed to demonstrate the presence of lymphatic vessels (LV) in the mucosa of in-situ (pTis) CRC, and of detectable tumour burden in regional LNs. This is an observational retrospective study of 39 surgically resected in situ CRCs. The number of LVs was evaluated in both pTis and normal mucosa using D2-40 immunostains. All LNs were assessed with both H&E and the One Step Nucleic Acid Amplification (OSNA) assay, and the results were correlated with clinicopathological features. D2-40 immunohistochemisty revealed LVs in the lamina propria of all pTis CRC (100%), being absent in normal mucosa. A median of 16 LNs were freshly dissected per patient, and all cases were pN0 with H&E. Molecular LN analysis with OSNA revealed the presence of low amounts of tumour burden in 11/39 (28%) cases (range 400 to 4270 CK19 mRNA copies/µL), which had no clinical consequences. This study demonstrates the presence of LVs in the lamina propria in 100% of pTis CRC, as well as the presence of low amounts of tumour burden in regional LNs, only detected by molecular methods. Given the prognostic value of LN tumour burden, its molecular quantification may help a patient's clinical management.
Collapse
Affiliation(s)
- Maria Teresa Rodrigo-Calvo
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain
- Molecular Pathology of Inflammatory Conditions and Solid Tumours Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
| | - Karmele Saez de Gordoa
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain
- Molecular Pathology of Inflammatory Conditions and Solid Tumours Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
| | - Sandra Lopez-Prades
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain
- Molecular Pathology of Inflammatory Conditions and Solid Tumours Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
| | - Ivan Archilla
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain
- Molecular Pathology of Inflammatory Conditions and Solid Tumours Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
| | - Alba Diaz
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain
- Molecular Pathology of Inflammatory Conditions and Solid Tumours Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Department of Basic Clinical Practice, University of Barcelona (UB), 08036 Barcelona, Spain
| | - Mario Berrios
- Pathology Department, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain
| | - Jordi Camps
- Molecular Pathology of Inflammatory Conditions and Solid Tumours Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Gastroenterology Department, Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain
- Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, University Autonomous of Barcelona, 08193 Bellaterra, Spain
| | - Eva Musulen
- Pathology Department, Hospital Universitari General de Catalunya-Grupo QuironSalud, Sant Cugat del Vallès, 08195 Barcelona, Spain
- Josep Carreras Leukaemia Research Institute, Badalona, 08916 Barcelona, Spain
- Correspondence: (E.M.); (M.C.); Tel.: +34-935047940 (E.M.); +34-932275536 (M.C.)
| | - Miriam Cuatrecasas
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain
- Molecular Pathology of Inflammatory Conditions and Solid Tumours Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Department of Basic Clinical Practice, University of Barcelona (UB), 08036 Barcelona, Spain
- Correspondence: (E.M.); (M.C.); Tel.: +34-935047940 (E.M.); +34-932275536 (M.C.)
| |
Collapse
|
|
7
|
Molecular Detection of Lymph Node Metastases in Lung Cancer Patients Using the One-Step Nucleic Acid Amplification Method:Clinical Significance and Prognostic Value. Cells 2022; 11:cells11244010. [PMID: 36552774 PMCID: PMC9776771 DOI: 10.3390/cells11244010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 12/01/2022] [Accepted: 12/08/2022] [Indexed: 12/14/2022] Open
Abstract
The one-step nucleic acid amplification (OSNA) method allows for the quantitative evaluation of the tumor burden in resected lymph nodes (LNs) in patients with lung cancer. This technique enables to detect macro and micrometastases, facilitating the correct classification of patients for appropriate follow-up of the disease after surgery. Of 160 patients with resectable lung cancer whose LNs were examined by OSNA, H&E and CK19 IHC between July 2015 and December 2018, 110 patients with clinical stages from IA1 to IIIB were selected for follow-up. LN staging in lung cancer by pathological study led to understaging in 13.64% of the cases studied. OSNA allowed to quantify the tumor burden and establish a prognostic value. Patients with a total tumor load of ≥1650 cCP/uL were associated with a significantly increased likelihood of recurrence. Moreover, the survival of patients with <4405 cCP/uL was significantly higher than patients with ≥4405 cCP/uL. The OSNA assay is a rapid and accurate technique for quantifying the tumor burden in the LNs of lung cancer patients and OSNA quantitative data could allow to establish prognostic values for recurrence-free survival and overall survival in this type of malignancy.
Collapse
|
|
8
|
Cytology Smears: An Enhanced Alternative Method for Colorectal Cancer pN Stage-A Multicentre Study. Cancers (Basel) 2022; 14:cancers14246072. [PMID: 36551559 PMCID: PMC9775901 DOI: 10.3390/cancers14246072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/01/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022] Open
Abstract
Stage II colorectal cancer (CRC) recurrence remains a clinical problem. Some of these patients are true stage III CRC with a pN0 pathology stage. This large prospective multicentre cohort study aimed at evaluating the diagnostic ability of lymph node (LN) cytology smears to perform the pN stage and compare it with the conventional haematoxylin and eosin (H&E) pathology pN stage. Additionally, we used the One-Step Nucleic Acid Amplification (OSNA), a high-sensitive molecular method of LN staging. A total of 3936 fresh LNs from 217 CRC surgical specimens were examined by three methods, H&E, LN cytology smears, and OSNA. H&E detected 29% of patients with positive LNs, cytology smears 35%, and OSNA 33.2% (p < 0.0001). H&E and cytology concordantly classified 92.2% of tumours, and 88.5% between OSNA and H&E. Cytology had 96.8% sensitivity and 90.3% specificity to discriminate positive/negative patients compared to H&E (p = 0.004), and 87.3% sensitivity and 89% specificity when compared to OSNA (p = 0.56). Patients with positive LNs detected by any of the three methods had significantly worse disease-free and overall survival. We conclude that pN stage accuracy for detecting positive LNs is superior with LN cytological smears than with conventional H&E, which would enable a better pN stage and management of early-stage CRC patients.
Collapse
|
|
9
|
Crafa F, Vanella S, Catalano OA, Pomykala KL, Baiamonte M. Role of one-step nucleic acid amplification in colorectal cancer lymph node metastases detection. World J Gastroenterol 2022; 28:4019-4043. [PMID: 36157105 PMCID: PMC9403438 DOI: 10.3748/wjg.v28.i30.4019] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 06/03/2022] [Accepted: 07/22/2022] [Indexed: 02/06/2023] Open
Abstract
Current histopathological staging procedures in colorectal cancer (CRC) depend on midline division of the lymph nodes (LNs) with one section of hematoxylin and eosin staining. Cancer cells outside this transection line may be missed, which could lead to understaging of Union for International Cancer Control Stage II high-risk patients. The one-step nucleic acid amplification (OSNA) assay has emerged as a rapid molecular diagnostic tool for LN metastases detection. It is a molecular technique that can analyze the entire LN tissue using a reverse-transcriptase loop-mediated isothermal amplification reaction to detect tumor-specific cytokeratin 19 mRNA. Our findings suggest that the OSNA assay has a high diagnostic accuracy in detecting metastatic LNs in CRC and a high negative predictive value. OSNA is a standardized, observer-independent technique, which may lead to more accurate staging. It has been suggested that in stage II CRC, the upstaging can reach 25% and these patients can access postoperative adjuvant chemotherapy. Moreover, intraoperative OSNA sentinel node evaluation may allow early CRC to be treated with organ-preserving surgery, while in more advanced-stage disease, a tailored lymphadenectomy can be performed considering the presence of aberrant lymphatic drainage and skip metastases.
Collapse
Affiliation(s)
- Francesco Crafa
- Division of General and Surgical Oncology, St. Giuseppe Moscati Hospital, Center of National Excellence and High Specialty, Avellino 83100, Italy
| | - Serafino Vanella
- Division of General and Surgical Oncology, St. Giuseppe Moscati Hospital, Center of National Excellence and High Specialty, Avellino 83100, Italy
| | - Onofrio A Catalano
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
| | - Kelsey L Pomykala
- Department of Nuclear Medicine, Department of Radiological Sciences, David Geffen School of Medicine at University of California, Los Angeles, University Hospital Essen, University of Duisburg-Essen, Essen 45141, Germany
| | - Mario Baiamonte
- Division of General and Surgical Oncology, St. Giuseppe Moscati Hospital, Center of National Excellence and High Specialty, Avellino 83100, Italy
| |
Collapse
|
|
10
|
Application of One-Step Nucleic Acid Amplification (OSNA) in different cancer entities and usefulness in prostate cancer: a systematic review. BMC Cancer 2022; 22:357. [PMID: 35366849 PMCID: PMC8976947 DOI: 10.1186/s12885-022-09355-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 01/28/2022] [Indexed: 12/24/2022] Open
Abstract
Background Lymph node (LN) status is a key prognostic factor in the decision-making process of different cancer entities, including prostate cancer (PCa). Sectioning and haematoxylin and eosin (H&E) staining technique remain the gold standard for the evaluation of LN metastases despite some limitations, especially low sensitivity in detecting an accurate tumour burden within the LN, as well as a subjective and time-consuming result. One-step nucleic acid amplification (OSNA) quantifies mRNA copies of cytokeratin 19 (CK19) in a fast, objective, automated, and reproducible way, raising a general interest to explore its utility for lymphatic metastasis identification in different malignancies. Methods To present the latest evidence related to the detection of LN metastases in several tumours by using OSNA compared with the conventional H&E method, a systematic review of articles published since March 2021 was conducted using PubMed, Cochrane Library, and Web of Science databases. References from primary papers and review articles were checked to obtain further potential studies. Our procedure for evaluating records identified during the literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. With the aim to design and justify future clinical routine use of OSNA in PCa, novel PCa evidence has been included in this review for the first time. Results Twenty five studies were included. LN from six different groups of tumours: breast, gastrointestinal, gynecological, lung, head and neck and prostate cancers has been assessed. OSNA was compared with post-operative formalin-fixed paraffin-embedded tissue sections with H&E staining as the reference standard. Contingency tables were created, and concordance rate, sensitivity, specificity and predictive values were reported. Seventeen studies analysed the discordant cases using different techniques. Conclusion OSNA method has a high diagnostic accuracy for the detection of LN metastases in several CK19 expressing tumours. Available evidence might encourage future investigations about its usage in PCa patients to improve LN staging and prognosis.
Collapse
|
|
11
|
Lutsyk M, Turgeman I, Bar-Sela G. Rapid Initiation of Neoadjuvant Chemoradiotherapy After Diagnosis is Associated With Improved Pathologic Response in Locally Advanced Rectal Cancer. Am J Clin Oncol 2022; 45:1-8. [PMID: 34857697 DOI: 10.1097/coc.0000000000000872] [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: 11/09/2022]
Abstract
INTRODUCTION In rectal cancer, neoadjuvant chemoradiation (NCRT) is preferred because of toxicity profile, improved resectability and sphincter preservation, although with no impact on overall survival. Pathologic complete response (pCR) to NCRT has been linked with longer disease-free survival (DFS). The study purpose was to evaluate an association between clinical factors and treatment schedule with tumor response and treatment outcome, among patients with locally advanced rectal cancer. PATIENTS AND METHODS In this single-center retrospective study, conducted over 9 years (2011 to 2020), patients with stage II to III rectal cancer who had received NCRT were enrolled. The standard radiotherapy was 45 Gy to the pelvis, with a simultaneous integrated 50 Gy boost to the primary tumor. Continuous 5-Fluorouracil or oral capecitabine was administered concurrently. Surgery was preplanned within 6 to 8 weeks. Multinomial logistic regressions for evaluation of clinical factors, Kaplan-Meier method for DFS estimation, and receiver operating characteristic analysis for determination of the optimal timeframe were used. RESULTS Of 279 cases, pCR was observed in 72 (25.8%). In 207 cases, pTis-4N-negative was obtained in 137 (66.2%), pT0N-positive in 6 (2.9%), and pTis-4N-positive in 64 (30.9%). The pCR group had shorter diagnosis-NCRT time (P<0.01) and on-treatment time (P=0.05). DFS was longer for pCR and partial responders with clinical stage II and III (P<0.0001). Diagnosis-NCRT time was shown different between pCR and non-pCR groups. receiver operating characteristic analysis (P<0.01) showed that a diagnosis-NCRT time of <4.5 weeks predicts pCR with a sensitivity of 88% and specificity of 81% accuracy. CONCLUSION The time elapsed between rectal cancer diagnosis and NCRT initiation is significantly associated with pCR. Reducing this time may increase the probability of achieving pCR.
Collapse
Affiliation(s)
| | | | - Gil Bar-Sela
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa
- Cancer Center, Emek Medical Center, Afula, Israel
| |
Collapse
|