|
1
|
Shahshenas S, Hosseini SM, Yarmohammadi H, Soltanipur M, Jalali Nadoushan M. Expression of cytokeratin 19 in prostatic adenocarcinoma: a systematic review. BMC Cancer 2025; 25:52. [PMID: 39789502 PMCID: PMC11720304 DOI: 10.1186/s12885-025-13456-x] [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: 07/31/2024] [Accepted: 01/06/2025] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND Cytokeratins are intracellular proteins known as diagnostic biomarkers or prognostic factors for certain cancers. Cytokeratin 19 (CK-19) expression has been proven to have prognostic value for some cancers, but its relationship with others, such as prostate cancer (PCa), remains unclear. This systematic review article aimed to examine the relationship between CK-19 expression and prostate adenocarcinoma (PAC). METHODS To include the eligible studies that detected CK-19 expression in PAC, published articles since June 2024 were found using PubMed, Scopus, and Web of Science databases. The "prostate cancer" and "cytokeratin 19" keywords and their Mesh term were used for search databases. Data from the included articles were extracted and tabulated. This study was performed using the PRISMA guidelines, and the JBI checklist was used for the quality assessment. The study protocol was registered in PROSPERO under the "CRD42023472637" code. RESULTS Twenty-one studies were included. Eleven studies used reverse transcription polymerase chain reaction (RT-PCR) to investigate CK-19 expression, four used immunohistochemistry (IHC) staining, three used both one-step nucleic acid amplification (OSNA) and hematoxylin and eosin (H&E) methods, and three used the electrochemiluminescence (ECL) technique. CK-19 expression was detected in 301 patients among 619 patients. Additionally, only five out of 80 healthy donors were positive for CK-19 expression. CONCLUSION Available evidence indicates a correlation between CK-19 expression and PAC progression, with higher CK-19 levels associated with advanced stages and worse prognosis. The overall evidence suggests that CK-19 could serve as a diagnostic and prognostic marker in PAC.
Collapse
Affiliation(s)
- Sina Shahshenas
- Student Research Committee, Faculty of Medicine, Shahed University, Tehran, Iran
| | - Seyyed Mohammad Hosseini
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Science (TUMS), Tehran, Iran
| | - Hossein Yarmohammadi
- Quality of Life Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
| | - Masood Soltanipur
- Quality of Life Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
| | | |
Collapse
|
|
2
|
Argun OB, Mourmouris P, Saglican Y, Doganca T, Tuna MB, Kayhan CK, Yalcinkaya O, Tufek I, Kara H, Obek C, Ince U, Tzelves L, Skolarikos A, Kural AR. One step nucleic acid amplification (OSNA) for detection of lymph node metastasis during robotic radical prostatectomy for prostate cancer: A pilot study. Arch Ital Urol Androl 2022; 94:265-269. [DOI: 10.4081/aiua.2022.3.265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 03/02/2022] [Indexed: 11/23/2022] Open
Abstract
Introduction: The OSNA technique is based on reverse transcription loop-mediated DNA amplification for the detection of cytokeratin 19 (CK19) messen-ger RNA (mRNA). The purpose of our paper, which represents the first study in the literature, is to test the accuracy of this method in the detection of lymph node metastases in patients undergoing robotic radical prostatectomy with lymph node dis-section. Methods: Our cohort consisted of patients that have undergone robotic radical prostatectomy with extended lymph node dissec-tion. Lymph nodes were evaluated with imprint technique and then with frozen section examination. The remaining tissue was evaluated by OSNA method. Lymph nodes were defined as ‘neg-ative’ or ‘positive’ according to mRNA copy number. Results: 7 patients and 25 lymph nodes were included in our cohort. Two patients were found negative with all pathology methods. In one patient the standard stains revealed a suspi-cious outcome but it was positive for micrometastasis with OSNA. In another patient the outcome was positive for standard stains and negative for OSNA. Finally, 2 patients were found positive for OSNA and negative for imprint methods. Conclusions: One Step Nucleic Acid Amplification (OSNA) method using CK19 seems to fail in detection of lymph node metastases in prostate cancer patients undergoing radical prostatectomy and lymph node dissection.
Collapse
|
|
3
|
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
|
|
4
|
Diestro MD, Berjón A, Zapardiel I, Yébenes L, Ruiz I, Lekuona A, Rezola M, Jaunarena I, Siegrist J, Sánchez-Pastor M, Cuadra M, Sagasta A, Guerra I, Lete LI, Roldán F, Marta CB, Boillos MJ, Cardiel MJ, López-de la Manzanara C, Relea F, Coronado PJ, Pascual A, Román MJ, Peiró G, Matute LJ, Montero B, Muruzábal JC, Guarch R, Zorrero C, Calatrava A, Ribot L, Costa I, Hernández A, Hardisson D. One-Step Nucleic Acid Amplification (OSNA) of Sentinel Lymph Node in Early-Stage Endometrial Cancer: Spanish Multicenter Study (ENDO-OSNA). Cancers (Basel) 2021; 13:4465. [PMID: 34503275 PMCID: PMC8431061 DOI: 10.3390/cancers13174465] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 08/31/2021] [Accepted: 09/02/2021] [Indexed: 12/24/2022] Open
Abstract
The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study, and 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1 mm portion of each lymph node was subjected to semi-serial sectioning at 200 μm intervals and examined by hematoxylin-eosin and immunohistochemistry with CK19; the remaining tissue was analyzed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/μL), the sensitivity of the OSNA assay was 92%, specificity was 82%, diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis.
Collapse
Affiliation(s)
- María Dolores Diestro
- Gynecologic Oncology Unit, Department of Gynecology and Obstetrics, Hospital Universitario La Paz, Hospital La Paz Institute for Health Research (IdiPAZ), Faculty of Medicine, Universidad Autónoma de Madrid, 28046 Madrid, Spain; (I.Z.); (J.S.); (M.S.-P.); (A.H.)
| | - Alberto Berjón
- Department of Pathology, Hospital Universitario La Paz, Molecular Pathology and Therapeutic Targets Group, Hospital La Paz Institute for Health Research (IdiPAZ), Center for Biomedical Research in the Cancer Network (Centro de Investigación Biomédica en Red de Cáncer, CIBERONC), Instituto de Salud Carlos III, Faculty of Medicine, Universidad Autónoma de Madrid, 28046 Madrid, Spain; (A.B.); (L.Y.)
| | - Ignacio Zapardiel
- Gynecologic Oncology Unit, Department of Gynecology and Obstetrics, Hospital Universitario La Paz, Hospital La Paz Institute for Health Research (IdiPAZ), Faculty of Medicine, Universidad Autónoma de Madrid, 28046 Madrid, Spain; (I.Z.); (J.S.); (M.S.-P.); (A.H.)
| | - Laura Yébenes
- Department of Pathology, Hospital Universitario La Paz, Molecular Pathology and Therapeutic Targets Group, Hospital La Paz Institute for Health Research (IdiPAZ), Center for Biomedical Research in the Cancer Network (Centro de Investigación Biomédica en Red de Cáncer, CIBERONC), Instituto de Salud Carlos III, Faculty of Medicine, Universidad Autónoma de Madrid, 28046 Madrid, Spain; (A.B.); (L.Y.)
| | - Irune Ruiz
- Department of Pathology, Hospital Universitario Donostia Osakidetza, 20014 Donostia, Spain; (I.R.); (M.R.)
| | - Arantza Lekuona
- Department of Gynecology, Hospital Universitario Donostia Osakidetza, 20014 Donostia, Spain; (A.L.); (I.J.)
| | - Marta Rezola
- Department of Pathology, Hospital Universitario Donostia Osakidetza, 20014 Donostia, Spain; (I.R.); (M.R.)
| | - Ibon Jaunarena
- Department of Gynecology, Hospital Universitario Donostia Osakidetza, 20014 Donostia, Spain; (A.L.); (I.J.)
| | - Jaime Siegrist
- Gynecologic Oncology Unit, Department of Gynecology and Obstetrics, Hospital Universitario La Paz, Hospital La Paz Institute for Health Research (IdiPAZ), Faculty of Medicine, Universidad Autónoma de Madrid, 28046 Madrid, Spain; (I.Z.); (J.S.); (M.S.-P.); (A.H.)
| | - Margarita Sánchez-Pastor
- Gynecologic Oncology Unit, Department of Gynecology and Obstetrics, Hospital Universitario La Paz, Hospital La Paz Institute for Health Research (IdiPAZ), Faculty of Medicine, Universidad Autónoma de Madrid, 28046 Madrid, Spain; (I.Z.); (J.S.); (M.S.-P.); (A.H.)
| | - María Cuadra
- Department of Gynecology, Instituto de Investigación Bioaraba, OSI Araba Hospital Universitario, 01009 Vitoria-Gasteiz, Spain; (M.C.); (L.I.L.)
| | - Amaia Sagasta
- Department of Pathology, Instituto de Investigación Bioaraba, OSI Araba Hospital Universitario, 01009 Vitoria-Gasteiz, Spain; (A.S.); (I.G.)
| | - Isabel Guerra
- Department of Pathology, Instituto de Investigación Bioaraba, OSI Araba Hospital Universitario, 01009 Vitoria-Gasteiz, Spain; (A.S.); (I.G.)
| | - Luis I. Lete
- Department of Gynecology, Instituto de Investigación Bioaraba, OSI Araba Hospital Universitario, 01009 Vitoria-Gasteiz, Spain; (M.C.); (L.I.L.)
| | - Fernando Roldán
- Department of Gynecology, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain; (F.R.); (M.J.B.)
| | - Carlo B. Marta
- Department of Pathology, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain; (C.B.M.); (M.J.C.)
| | - María J. Boillos
- Department of Gynecology, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain; (F.R.); (M.J.B.)
| | - María J. Cardiel
- Department of Pathology, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain; (C.B.M.); (M.J.C.)
| | - Carlos López-de la Manzanara
- Department of Gynecology, Hospital General Universitario Ciudad Real, Universidad de Castilla-La Mancha, 13005 Ciudad Real, Spain;
| | - Fernanda Relea
- Department of Pathology, Hospital General Universitario Ciudad Real, Universidad de Castilla-La Mancha, 13005 Ciudad Real, Spain;
| | - Pluvio J. Coronado
- Women Health Institute, Hospital Clínico Universitario San Carlos, IdISSC, Complutense University, 28040 Madrid, Spain;
| | - Alejandro Pascual
- Department of Pathology, Hospital Clínico Universitario San Carlos, 28040 Madrid, Spain;
| | - María J. Román
- Department of Gynecology, Hospital General Universitario Alicante and Alicante Institute for Health and Biomedical Research (ISABIAL), 03010 Alicante, Spain;
| | - Gloria Peiró
- Department of Pathology, Hospital General Universitario Alicante and Alicante Institute for Health and Biomedical Research (ISABIAL), 03010 Alicante, Spain;
| | - Luis J. Matute
- Department of Gynecology, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain;
| | - Beatriz Montero
- Department of Pathology, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain;
| | - Juan C. Muruzábal
- Department of Gynecology, Complejo Hospitalario Universitario Navarra, 31008 Pamplona, Spain;
| | - Rosa Guarch
- Department of Pathology, Complejo Hospitalario Universitario Navarra, 31008 Pamplona, Spain;
| | - Cristina Zorrero
- Department of Gynecology, Hospital Fundación IVO, 46009 Valencia, Spain;
| | - Ana Calatrava
- Department of Pathology, Hospital Fundación IVO, 46009 Valencia, Spain;
| | - Laia Ribot
- Department of Gynecology, Corporación Sanitaria Parc Taulí Sabadell, 08208 Barcelona, Spain;
| | - Irmgard Costa
- Department of Pathology, Corporación Sanitaria Parc Taulí Sabadell, 08208 Barcelona, Spain;
| | - Alicia Hernández
- Gynecologic Oncology Unit, Department of Gynecology and Obstetrics, Hospital Universitario La Paz, Hospital La Paz Institute for Health Research (IdiPAZ), Faculty of Medicine, Universidad Autónoma de Madrid, 28046 Madrid, Spain; (I.Z.); (J.S.); (M.S.-P.); (A.H.)
| | - David Hardisson
- Department of Pathology, Hospital Universitario La Paz, Molecular Pathology and Therapeutic Targets Group, Hospital La Paz Institute for Health Research (IdiPAZ), Center for Biomedical Research in the Cancer Network (Centro de Investigación Biomédica en Red de Cáncer, CIBERONC), Instituto de Salud Carlos III, Faculty of Medicine, Universidad Autónoma de Madrid, 28046 Madrid, Spain; (A.B.); (L.Y.)
| |
Collapse
|
|
5
|
Weixler B, Teixeira da Cunha S, Warschkow R, Demartines N, Güller U, Zettl A, Vahrmeijer A, van de Velde CJH, Viehl CT, Zuber M. Molecular Lymph Node Staging with One-Step Nucleic Acid Amplification and its Prognostic Value for Patients with Colon Cancer: The First Follow-up Study. World J Surg 2021; 45:1526-1536. [PMID: 33512566 PMCID: PMC8026461 DOI: 10.1007/s00268-020-05949-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2020] [Indexed: 01/11/2023]
Abstract
Background Molecular lymph node workup with one-step nucleic acid amplification (OSNA) is a validated diagnostic adjunct in breast cancer and also appealing for colon cancer (CC) staging. This study, for the first time, evaluates the prognostic value of OSNA in CC. Patients and methods The retrospective study includes patients with stage I-III CC from three centres. Lymph nodes were investigated with haematoxylin and eosin (H&E) and with OSNA, applying a 250 copies/μL threshold of CK19 mRNA. Diagnostic value of H&E and OSNA was assessed by survival analysis, sensitivity, specificity and time-dependent receiver operating characteristic curves. Results Eighty-seven patients were included [mean follow-up 53.4 months (± 24.9)]. Disease recurrence occurred in 16.1% after 19.8 months (± 12.3). Staging with H&E independently predicted worse cancer-specific survival in multivariate analysis (HR = 10.77, 95% CI 1.07–108.7, p = 0.019) but not OSNA (HR = 3.08, 95% CI 0.26–36.07, p = 0.197). With cancer-specific death or recurrence as gold standard, H&E sensitivity was 46.7% (95% CI 21.3–73.4%) and specificity 84.7% (95% CI 74.3–92.1%). OSNA sensitivity and specificity were 60.0% (95% CI 32.3–83.7%) and 75.0% (95% CI 63.4–84.5%), respectively. Conclusions In patients with CC, OSNA does not add relevant prognostic value to conventional H&E contrasting findings in other cancers. Further studies should assess lower thresholds for OSNA (< 250 copies/μL).
Collapse
Affiliation(s)
- Benjamin Weixler
- Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands.,Department of General, Visceral and Vascular Surgery, Charité University Hospital, Campus Benjamin Franklin, Berlin, Germany
| | | | - René Warschkow
- Department of Surgery, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Nicolas Demartines
- Department of Surgery, Vaudois University Hospital Centre, Lausanne, Switzerland
| | - Ulrich Güller
- Department of Oncology, Spital STS AG, Thun, Switzerland
| | - Andreas Zettl
- Department of Pathology, Viollier AG, Basel, Switzerland
| | - Alexander Vahrmeijer
- Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands
| | | | - Carsten T Viehl
- Department of Surgery, Hospital Centre Biel, Biel, Switzerland
| | - Markus Zuber
- Department of Surgery, Cantonal Hospital Olten, Olten, Switzerland. .,Visceral Surgery Centre Clarunis, St. Clara Hospital and University Hospital Basel, University of Basel, Spitalstrasse 21, CH-4031, Basel, Switzerland.
| |
Collapse
|
|
6
|
Wang X, Zheng X, Zhu J, Li Z, Wei T. The Diagnostic Accuracy of One-Step Nucleic Acid Amplification for Lymph Node Metastases of Papillary Thyroid Carcinoma： A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne) 2021; 12:757766. [PMID: 35058876 PMCID: PMC8764176 DOI: 10.3389/fendo.2021.757766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 12/06/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND One-step nucleic acid amplification (OSNA) analysis is a molecular diagnostic technique for lymph node metastases (LNMs) by quantifying cytokeratin 19(CK 19) mRNA. We aim to evaluate the intraoperative diagnostic accuracy of OSNA assay for LNMs of papillary thyroid carcinoma (PTC). METHODS PubMed, Embase, Cochrane Library, and Web of Science databases were searched to retrieve related literature. A meta-analysis was performed using STATA11.0, Meta-Disc 1.4 and RevMan 5.3. RESULTS This meta-analysis included six studies involving 987 lymph nodes from 194 patients. The pooled sensitivity, specificity, and area under the summary receiver-operating characteristic curve (AUC) of OSNA for detecting LNM were 0.88, 0.90, and 0.95, respectively. CONCLUSION OSNA assay is an accurate molecular diagnosis for intraoperative detection of lymph node metastasis in PTC.
Collapse
|
|
7
|
Hiyoshi Y, Akiyoshi T, Fukunaga Y. The advantage of one-step nucleic acid amplification for the diagnosis of lymph node metastasis in colorectal cancer patients. Ann Gastroenterol Surg 2021; 5:60-66. [PMID: 33532681 PMCID: PMC7832960 DOI: 10.1002/ags3.12392] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 07/28/2020] [Accepted: 08/01/2020] [Indexed: 12/20/2022] Open
Abstract
Generally, the postoperative examination of lymph nodes (LNs) is based on a microscopic examination of one hematoxylin and eosin (HE)-stained slide; however, an examination of only one part of the LN might lead to incorrect staging of the tumor due to tissue allocation bias. Although multilevel sectioning and the use of immunohistochemistry (IHC) have improved the detection of micrometastases in LNs, this approach is laborious, time-consuming, and costly. A novel molecular technique for the detection of LN metastases of tumors, called one-step nucleic acid amplification (OSNA), is a rapid and semi-quantitative examination quantifying the number of cytokeratin 19 (CK-19) mRNA copies derived from a tumor. OSNA is already in clinical use for the diagnosis of LN metastasis in breast cancer patients; however, the use of OSNA is under investigation with promising results for colorectal cancer (CRC). The present review assessed recent studies on OSNA vs a histopathological examination and its implications for CRC staging and treatment. A total of 16 studies of OSNA in CRC yielded by a PubMed search were reviewed. Among them, seven studies evaluating the diagnostic performance revealed that OSNA had a high specificity (96.8%), high concordance rate (96.0%), and negative predictive value (98.6%) in a pooled assessment. In addition, four studies examining the utility of OSNA in sentinel LNs (SLNs) and two studies focusing on upstaging in pathologically node-negative CRC patients were also reviewed. Multicenter prospective studies with a large cohort of CRC patients are warranted to reveal the benefits of OSNA in the future.
Collapse
Affiliation(s)
- Yukiharu Hiyoshi
- Gastroenterological CenterDepartment of Gastroenterological SurgeryThe Cancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyoJapan
| | - Takashi Akiyoshi
- Gastroenterological CenterDepartment of Gastroenterological SurgeryThe Cancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyoJapan
| | - Yosuke Fukunaga
- Gastroenterological CenterDepartment of Gastroenterological SurgeryThe Cancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyoJapan
| |
Collapse
|
|
8
|
Evaluation of the prognostic relevance of the recommended minimum number of lymph nodes in colorectal cancer-a propensity score analysis. Int J Colorectal Dis 2021; 36:779-789. [PMID: 33454816 PMCID: PMC7952332 DOI: 10.1007/s00384-021-03835-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/05/2021] [Indexed: 02/08/2023]
Abstract
PURPOSE Nodal status in colorectal cancer (CRC) is an important prognostic factor, and adequate lymph node (LN) staging is crucial. Whether the number of resected and analysed LN has a direct impact on overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) is much discussed. Guidelines request a minimum number of 12 LN to be analysed. Whether that threshold marks a prognostic relevant cut-off remains unknown. METHODS Patients operated for stage I-III CRC were identified from a prospectively maintained database. The impact of the number of analysed LN on OS, CSS and DFS was assessed using Cox regression and propensity score analysis. RESULTS Of the 687 patients, 81.8% had ≥ 12 LN resected and analysed. Median LN yield was 17.0 (IQR 13.0-23.0). Resection and analysis of ≥ 12 LN was associated with improved OS (HR = 0.73, 95% CI: 0.56-0.95, p = 0.033), CSS (HR 0.52, 95% CI: 0.31-0.85, p = 0.030) and DFS (HR = 0.73, 95% CI: 0.57-0.95, p = 0.030) in multivariate Cox analysis. After adjusting for biasing factors with propensity score matching, resection of ≥ 12 LN was significantly associated with improved OS (HR = 0.59; 95% CI: 0.43-0.81; p = 0.002), CSS (HR = 0.34; 95% CI: 0.20-0.60; p < 0.001) and DFS (HR = 0.55; 95% CI: 0.41-0.74; p < 0.001) compared to patients with < 12 LN. CONCLUSION Eliminating biasing factors by a propensity score matching analysis underlines the prognostic importance of the number of analysed LN. The set threshold marks the minimum number of required LN but nevertheless represents a cut-off regarding outcome in stage I-III CRC. This analysis therefore highlights the significance and importance of adherence to surgical oncological standards.
Collapse
|
|
9
|
The evolving role of one-step nucleic acid amplification (OSNA) for the intra-operative detection of lymph node metastases: A diagnostic accuracy meta-analysis. Eur J Surg Oncol 2020; 47:1233-1243. [PMID: 33309549 DOI: 10.1016/j.ejso.2020.12.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 11/21/2020] [Accepted: 12/01/2020] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND One Step Nucleic Acid Amplification (OSNA) assay has recently emerged as a rapid molecular diagnostic tool for the detection of lymph node (LN) metastases. It is a molecular technique that analyses the entire LN tissue using a reverse-transcriptase loop-mediated isothermal amplification reaction to detect tumour specific cytoceratin 19 mRNA. AIM To ascertain the diagnostic accuracy of OSNA assay in detecting LN metastases amongst different types of malignancy. DESIGN We systematically searched MEDLINE, SCOPUS, ClinicalTrials.gov, and Cochrane Database, from inception up to August 2020. Quality assessment was performed using the Modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). We calculated pooled diagnostic indices using the random-effects model. Meta-regression and sub-group analyses were performed to address heterogeneity. RESULTS 31 studies were included in this meta-analysis, including four different types of cancer. The risk of bias and the overall quality of included studies was moderate to high. There was no evidence of publication bias. The pooled diagnostic odds ratio (DOR) for detecting LN metastases in gynaecological, head & neck/thyroid, gastrointestinal and lung cancer were 100.38, 76.17, 275.14, and 305.84, respectively. CONCLUSIONS Our findings suggest that OSNA assay had a high diagnostic accuracy in detecting metastatic LNs in different types of malignancy. This evidence is constrained by the limited studies available for few tumour types and the rather high heterogeneity for few outcomes.
Collapse
|
|
10
|
Peigné L, Godey F, Le Gallo M, Le Gall F, Fautrel A, Morcet J, Jégoux F. One-step nucleic acid amplification for detecting lymph node metastasis of head and neck squamous cell carcinoma. Oral Oncol 2020; 102:104553. [PMID: 32004908 DOI: 10.1016/j.oraloncology.2019.104553] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 12/21/2019] [Indexed: 01/11/2023]
Abstract
BACKGROUND In head and neck squamous cell carcinoma (HNSCC) 30% of cN0 patients have occult metastasis. LN invasion is a major prognostic factor. Sentinel lymph node (SLN) is an option for cN0 neck management. One-step nucleic acid amplification (OSNA) used to analyze SLN in breast cancer is also a candidate to get more reliable intraoperative HNSCC lymph node (LN) staging. OBJECTIVE To compare OSNA analysis to pathological analysis in cN0 HNSCC. MATERIALS AND METHODS 157 LN from 26 cN0 HNSCC patients were prospectively analyzed (6.3LN/patient). Exclusion criteria were previous surgery or radiotherapy. Each node was cut into 4 equal pieces alternatively sent to pathological analysis and OSNA technique. IHC CK19 was performed on the primary tumor biopsy and RT-qPCR of CK19, PVA and EPCAM on the LN lysate of discordant cases. RESULTS OSNA was able to provide intraoperative result in all patients. OSNA detected 21 metastases. There were 139 concordant LN (88.5%). There were 18 initial discordant LN (11.5%), 13 (8.3%) were OSNA positive/pathological analysis negative, 5 (3.2%) were OSNA negative/pathological analysis positive. After elimination of allocation bias, false negative rate was 1.3%, sensitivity and specificity were 90% and 95.6%, PPV and NPV were 75% and 98.5%. CONCLUSION Our results suggest that OSNA should be considered to improve SNB analysis both for increasing micro metastasis diagnosis and offer extemporaneous results. Study registered under clinicaltrials.gov database number NCT02852343.
Collapse
Affiliation(s)
- Lucie Peigné
- Head Neck Surgery Department, University Hospital, Rennes, France
| | - Florence Godey
- Department of Biology, Eugène Marquis Comprehensive Cancer Center, CS 44 229, Av. De Bataille Flandres Dunkerques, 35042 Rennes Cedex, France
| | - Mathieu Le Gallo
- Chemistry, Oncogenesis, Stress, Signaling COSS, INSERM 1242, Rennes 1 University, CLCC Eugene Marquis, Rue de la bataille Flandres Dunkerques, Rennes, France
| | - François Le Gall
- Pathology Department, University Hospital, Rennes, France; Head Neck Surgery Department, University Hospital, Rennes, France
| | - Alain Fautrel
- H2P2, Histopathological Platform, University of Rennes, 35000 Rennes, France
| | - Jeff Morcet
- Clinical Investigation Center, CIC INSERM 1414, University Hospital of Rennes, France
| | - Franck Jégoux
- Head Neck Surgery Department, University Hospital, Rennes, France; Chemistry, Oncogenesis, Stress, Signaling COSS, INSERM 1242, Rennes 1 University, CLCC Eugene Marquis, Rue de la bataille Flandres Dunkerques, Rennes, France.
| |
Collapse
|
|
11
|
Itabashi M, Yamamoto H, Tomita N, Inomata M, Murata K, Hayashi S, Miyake Y, Igarashi S, Kato T, Noura S, Furuhata T, Ozawa H, Takemasa I, Yasui M, Takeyama H, Okamura S, Ohno Y, Matsuura N. Lymph Node Positivity in One-Step Nucleic Acid Amplification is a Prognostic Factor for Postoperative Cancer Recurrence in Patients with Stage II Colorectal Cancer: A Prospective, Multicenter Study. Ann Surg Oncol 2019; 27:1077-1083. [PMID: 31722072 PMCID: PMC7060165 DOI: 10.1245/s10434-019-07971-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Indexed: 01/11/2023]
Abstract
Background For colorectal cancer (CRC) patients, the standard histological lymph node (LN) evaluation has low sensitivity. Our previously developed one-step nucleic acid amplification (OSNA™) assay measures cytokeratin 19 gene expression in whole LNs. We recently showed that 17.6% of pN0 stage II CRC patients were OSNA positive, suggesting a correlation between OSNA results and disease recurrence. This multicenter, prospective study investigateed the prognostic value of the OSNA assay for pStage II CRC patients. Methods We examined 204 CRC patients who were preoperatively diagnosed as cN0 and cN1 and surgically treated at 11 medical institutions across Japan. Nine patients were excluded, and 195 patients (Stage I: n = 50, Stage II: n = 70, Stage III: n = 75) were examined. All LNs, harvested from patients, were examined histopathologically using one-slice hematoxylin–eosin staining. Furthermore, half of the LNs was examined by the OSNA assay. Patients were classified according to the UICC staging criteria and OSNA results, and the 3-year, disease-free survival (DFS) of each cohort was analyzed. Results Average 21.2 LNs/patient were subject to pathological examination. Approximately half of all harvested LNs (average, 9.4 LNs/patient) were suitable for the OSNA assay. Significantly lower 3-year DFS rates were observed in pStage (pathological Stage) II OSNA-positive patients than in OSNA-negative patients (p = 0.005). Among all assessed clinical and pathological parameters, only the OSNA result significantly affected 3-year DFS rates in pStage II CRC patients (p = 0.027). Conclusions This study shows that OSNA positivity is a risk factor for recurrence of the patients with pStage II CRC. Electronic supplementary material The online version of this article (10.1245/s10434-019-07971-y) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Michio Itabashi
- Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku, Japan
| | - Hirofumi Yamamoto
- Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Japan.
| | - Naohiro Tomita
- Division of Lower GI Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Masafumi Inomata
- Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine, Oita University, Oita, Japan
| | - Kohei Murata
- Department of Surgery, Kansai Rosai Hospital, Amagasaki, Japan
| | - Shigeoki Hayashi
- Department of Digestive Surgery, Nihon University Hospital, Chiyoda, Japan
| | - Yasuhiro Miyake
- Department of Surgery, Osaka Minato Central Hospital, Osaka, Japan
| | - Seiji Igarashi
- Division of Pathology, Tsuboi Cancer Center Hospital, Koriyama, Japan
| | - Takeshi Kato
- Department of Colorectal Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Shingo Noura
- Department of Surgery, Osaka Rosai Hospital, Sakai, Japan
| | - Tomohisa Furuhata
- Division of Gastroenterological and General Surgery, St. Marianna University Toyoko Hospital, Kawasaki, Japan
| | - Heita Ozawa
- Department of Colorectal Surgery, Tochigi Cancer Center, Utsunomiya, Japan
| | - Ichiro Takemasa
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, Japan
| | - Masayoshi Yasui
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | | | - Shu Okamura
- Department of Surgery, Suita Municipal Hospital, Suita, Japan
| | - Yuko Ohno
- Department of Mathematical Health Science, Graduate School of Medicine, Osaka University, Suita, Japan
| | | |
Collapse
|
|
12
|
Diaz-Mercedes S, Archilla I, Camps J, de Lacy A, Gorostiaga I, Momblan D, Ibarzabal A, Maurel J, Chic N, Bombí JA, Balaguer F, Castells A, Aldecoa I, Borras JM, Cuatrecasas M. Budget Impact Analysis of Molecular Lymph Node Staging Versus Conventional Histopathology Staging in Colorectal Carcinoma. APPLIED HEALTH ECONOMICS AND HEALTH POLICY 2019; 17:655-667. [PMID: 31115896 PMCID: PMC6748889 DOI: 10.1007/s40258-019-00482-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/09/2023]
Abstract
BACKGROUND The presence of lymph node (LN) metastasis is a critical prognostic factor in colorectal cancer (CRC) patients and is also an indicator for adjuvant chemotherapy. The gold standard (GS) technique for LN diagnosis and staging is based on the analysis of haematoxylin and eosin (H&E)-stained slides, but its sensitivity is low. As a result, patients may not be properly diagnosed and some may have local recurrence or distant metastases after curative-intent surgery. Many of these diagnostic and treatment problems could be avoided if the one-step nucleic acid amplification assay (OSNA) was used rather than the GS technique. OSNA is a fast, automated, standardised, highly sensitive, quantitative technique for detecting LN metastases. OBJECTIVES The aim of this study was to assess the budget impact of introducing OSNA LN analysis in early-stage CRC patients in the Spanish National Health System (NHS). METHODS A budget impact analysis comparing two scenarios (GS vs. OSNA) was developed within the Spanish NHS framework over a 3-year time frame (2017-2019). The patient population consisted of newly diagnosed CRC patients undergoing surgical treatment, and the following costs were included: initial surgery, pathological diagnosis, staging, follow-up expenses, systemic treatment and surgery after recurrence. One- and two-way sensitivity analyses were performed. RESULTS Using OSNA instead of the GS would have saved €1,509,182, €6,854,501 and €10,814,082 during the first, second and third years of the analysis, respectively, because patients incur additional costs in later years, leading to savings of more than €19 million for the NHS over the 3-year time horizon. CONCLUSIONS Introducing OSNA in CRC LN analysis may represent not only an economic benefit for the NHS but also a clinical benefit for CRC patients since a more accurate staging could be performed, thus avoiding unnecessary treatments.
Collapse
Affiliation(s)
- Sherley Diaz-Mercedes
- Pathology Department-Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain
| | - Ivan Archilla
- Pathology Department-Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain
| | - Jordi Camps
- Gastroenterology Department, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
- CIBERehd and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Hospital Clinic, Barcelona, Spain
| | | | - Iñigo Gorostiaga
- Pathology Department, Araba University Hospital, Vitoria-Gasteiz, Spain
| | - Dulce Momblan
- Surgical Department, Hospital Clinic, Barcelona, Spain
| | | | - Joan Maurel
- Medical Oncology Department, Hospital Clinic of Barcelona, Translational Genomics and Targeted Therapeutics in Solid Tumors Group, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Nuria Chic
- Medical Oncology Department, Hospital Clinic of Barcelona, Translational Genomics and Targeted Therapeutics in Solid Tumors Group, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Josep Antoni Bombí
- Pathology Department-Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain
| | - Francesc Balaguer
- Gastroenterology Department, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
- CIBERehd and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Hospital Clinic, Barcelona, Spain
| | - Antoni Castells
- Gastroenterology Department, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
- CIBERehd and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Hospital Clinic, Barcelona, Spain
| | - Iban Aldecoa
- Pathology Department-Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain
- Neurological Tissue Bank of the Biobank Clinic-IDIBAPS-XBTC, Hospital Clinic, Barcelona, Spain
| | - Josep Maria Borras
- Department of Clinical Sciences and Bellvitge Biomedical Research Institute (IDIBELL), Universitat de Barcelona, Barcelona, Spain
| | - Miriam Cuatrecasas
- Pathology Department-Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain.
- Pathology Department, Araba University Hospital, Vitoria-Gasteiz, Spain.
- CIBERehd and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Hospital Clinic, Barcelona, Spain.
| |
Collapse
|
|
13
|
Esposito F, Noviello A, Moles N, Coppola Bottazzi E, Baiamonte M, Macaione I, Ferbo U, Lepore M, Miro A, Crafa F. Sentinel Lymph Node Analysis in Colorectal Cancer Patients Using One-Step Nucleic Acid Amplification in Combination With Fluorescence and Indocyanine Green. Ann Coloproctol 2019; 35:174-180. [PMID: 31487764 PMCID: PMC6732328 DOI: 10.3393/ac.2018.07.21.1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Accepted: 07/21/2018] [Indexed: 02/06/2023] Open
Abstract
PURPOSE Analysis of the sentinel lymph node (SLN) in colorectal cancer (CRC) patients was proposed for more accurate staging and tailored lymphadenectomy. The aim of this study was to assess the ability to predict lymph node (LN) involvement through analysis of the SLN with a one-step nucleic acid (OSNA) technique in combination with peritumoral injection of indocyanine green (ICG) and near-infrared (NIR) lymphangiography in CRC patients. METHODS A total of 34 patients were enrolled. Overall, 51 LNs were analyzed with OSNA. LNs of 17 patients (50%) were examined simultaneously with hematoxylin and eosin (H&E) and OSNA. RESULTS SLN analysis of 17 patients examined with H&E and OSNA revealed that OSNA had a higher sensitivity (1 vs. 0.55), higher negative predictive value (1 vs. 0.66) and higher accuracy (100% vs. 76.4%) in predicting LN involvement. Overall, OSNA showed a sensitivity of 0.69, specificity of 1, accuracy of 88.2%, and stage migration of 8.8%. Compared to those who were OSNA (-), OSNA (+) patients had a greater number of LN metastases (4.8 vs. 0.16, P = 0.04), higher G3 rate (44.4% vs. 4%, P = 0.01), more advanced stage of disease (stage III: 77.8% vs. 16%; P = 0.00) and were more rapidly subjected to adjuvant chemotherapy (39.1 days vs. 50.2 days, P = 0.01). CONCLUSION SLN analysis with OSNA in combination with ICG-NIR lymphangiography is feasible and can detect LN involvement in CRC patients. Furthermore, it allows for more accurate staging reducing the delay between surgery and adjuvant chemotherapy.
Collapse
Affiliation(s)
- Francesco Esposito
- Oncological and General Surgery Unit, St. Giuseppe Moscati Hospital of National Relevance and High Specialty, Avellino, Italy
| | - Adele Noviello
- Oncological and General Surgery Unit, St. Giuseppe Moscati Hospital of National Relevance and High Specialty, Avellino, Italy
| | - Nicola Moles
- Oncological and General Surgery Unit, St. Giuseppe Moscati Hospital of National Relevance and High Specialty, Avellino, Italy
| | - Enrico Coppola Bottazzi
- Oncological and General Surgery Unit, St. Giuseppe Moscati Hospital of National Relevance and High Specialty, Avellino, Italy
| | - Mario Baiamonte
- General and Emergency Surgery Unit, Civico Benfratelli Di Cristina Hospital, Palermo, Italy
| | - Ina Macaione
- Department of Surgical, Oncological and Stomatological Disciplines, University of Palermo, Palermo, Italy
| | - Umberto Ferbo
- Institute of Pathology, St. Giuseppe Moscati Hospital of National Relevance and High Specialty, Avellino, Italy
| | - Maria Lepore
- Institute of Pathology, St. Giuseppe Moscati Hospital of National Relevance and High Specialty, Avellino, Italy
| | - Antonio Miro
- Oncological and General Surgery Unit, St. Giuseppe Moscati Hospital of National Relevance and High Specialty, Avellino, Italy
| | - Francesco Crafa
- Oncological and General Surgery Unit, St. Giuseppe Moscati Hospital of National Relevance and High Specialty, Avellino, Italy
| |
Collapse
|