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Metasin—An Intra-Operative RT-qPCR Assay to Detect Metastatic Breast Cancer in Sentinel Lymph Nodes
Nodal status is one of the most important prognostic factors in breast cancer. Established tests such as touch imprint cytology and frozen sections currently used in the intra-operative setting show variations in sensitivity and specificity. This limitation has led to the development of molecular al...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Diversity Preservation International (MDPI)
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742166/ https://www.ncbi.nlm.nih.gov/pubmed/23797656 http://dx.doi.org/10.3390/ijms140712931 |
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author | Al-Ramadhani, Salma Sai-Giridhar, Priya George, Dilushana Gopinath, Preethi Arkoumani, Evdokia Jader, Samar Sundaresan, Maryse Salgado, Roberto Larsimont, Dennis Bustin, Stephen A. Sundaresan, Vasi |
author_facet | Al-Ramadhani, Salma Sai-Giridhar, Priya George, Dilushana Gopinath, Preethi Arkoumani, Evdokia Jader, Samar Sundaresan, Maryse Salgado, Roberto Larsimont, Dennis Bustin, Stephen A. Sundaresan, Vasi |
author_sort | Al-Ramadhani, Salma |
collection | PubMed |
description | Nodal status is one of the most important prognostic factors in breast cancer. Established tests such as touch imprint cytology and frozen sections currently used in the intra-operative setting show variations in sensitivity and specificity. This limitation has led to the development of molecular alternatives, such as GeneSearch, a commercial intra-operative real-time quantitative Polymerase Chain Reaction (RT-qPCR) assay that allows the surgeon to carry out axillary clearance as a one-step process. Since GeneSearch has been discontinued, we have developed the replacement Metasin assay, which targets the breast epithelial cell markers CK19 and mammaglobin mRNA and identifies metastatic disease in sentinel lymph nodes. The optimised assay can be completed within 32 min (6 min for RNA preparation and 26 min instrument run time), making its use feasible in the intraoperative setting. An analysis by Metasin of 154 archived lymph node homogenates previously analysed by both parallel histology and GeneSearch showed concordance for 148 cases. The sensitivity and specificity of Metasin compared with GeneSearch were 95% (CI 83%–99%) and 97% (CI 91%–99%) respectively; compared with histology they were 95% (CI 83%–99%) and 97% (CI 91%–99%), respectively. The sensitivity and specificity of GeneSearch compared with histology were 90% (CI 77%–96%) and 97% (CI 93%–99%) respectively. The positive predictive value of Metasin was 90% and negative predictive value was 98% for both histology and GeneSearch. The positive predictive value of GeneSearch was 92% and the negative predictive value was 97% compared to histology. The discordance rates of Metasin with both GeneSearch and histology were 3.89%. In comparison, the discordance rate of GeneSearch with histology was 4.5%. Metasin’s robustness was independently evaluated on 193 samples previously analysed by GeneSearch from the Jules Bordet Institute, where Metasin yielded comparable results. |
format | Online Article Text |
id | pubmed-3742166 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Molecular Diversity Preservation International (MDPI) |
record_format | MEDLINE/PubMed |
spelling | pubmed-37421662013-08-13 Metasin—An Intra-Operative RT-qPCR Assay to Detect Metastatic Breast Cancer in Sentinel Lymph Nodes Al-Ramadhani, Salma Sai-Giridhar, Priya George, Dilushana Gopinath, Preethi Arkoumani, Evdokia Jader, Samar Sundaresan, Maryse Salgado, Roberto Larsimont, Dennis Bustin, Stephen A. Sundaresan, Vasi Int J Mol Sci Article Nodal status is one of the most important prognostic factors in breast cancer. Established tests such as touch imprint cytology and frozen sections currently used in the intra-operative setting show variations in sensitivity and specificity. This limitation has led to the development of molecular alternatives, such as GeneSearch, a commercial intra-operative real-time quantitative Polymerase Chain Reaction (RT-qPCR) assay that allows the surgeon to carry out axillary clearance as a one-step process. Since GeneSearch has been discontinued, we have developed the replacement Metasin assay, which targets the breast epithelial cell markers CK19 and mammaglobin mRNA and identifies metastatic disease in sentinel lymph nodes. The optimised assay can be completed within 32 min (6 min for RNA preparation and 26 min instrument run time), making its use feasible in the intraoperative setting. An analysis by Metasin of 154 archived lymph node homogenates previously analysed by both parallel histology and GeneSearch showed concordance for 148 cases. The sensitivity and specificity of Metasin compared with GeneSearch were 95% (CI 83%–99%) and 97% (CI 91%–99%) respectively; compared with histology they were 95% (CI 83%–99%) and 97% (CI 91%–99%), respectively. The sensitivity and specificity of GeneSearch compared with histology were 90% (CI 77%–96%) and 97% (CI 93%–99%) respectively. The positive predictive value of Metasin was 90% and negative predictive value was 98% for both histology and GeneSearch. The positive predictive value of GeneSearch was 92% and the negative predictive value was 97% compared to histology. The discordance rates of Metasin with both GeneSearch and histology were 3.89%. In comparison, the discordance rate of GeneSearch with histology was 4.5%. Metasin’s robustness was independently evaluated on 193 samples previously analysed by GeneSearch from the Jules Bordet Institute, where Metasin yielded comparable results. Molecular Diversity Preservation International (MDPI) 2013-06-24 /pmc/articles/PMC3742166/ /pubmed/23797656 http://dx.doi.org/10.3390/ijms140712931 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Al-Ramadhani, Salma Sai-Giridhar, Priya George, Dilushana Gopinath, Preethi Arkoumani, Evdokia Jader, Samar Sundaresan, Maryse Salgado, Roberto Larsimont, Dennis Bustin, Stephen A. Sundaresan, Vasi Metasin—An Intra-Operative RT-qPCR Assay to Detect Metastatic Breast Cancer in Sentinel Lymph Nodes |
title | Metasin—An Intra-Operative RT-qPCR Assay to Detect Metastatic Breast Cancer in Sentinel Lymph Nodes |
title_full | Metasin—An Intra-Operative RT-qPCR Assay to Detect Metastatic Breast Cancer in Sentinel Lymph Nodes |
title_fullStr | Metasin—An Intra-Operative RT-qPCR Assay to Detect Metastatic Breast Cancer in Sentinel Lymph Nodes |
title_full_unstemmed | Metasin—An Intra-Operative RT-qPCR Assay to Detect Metastatic Breast Cancer in Sentinel Lymph Nodes |
title_short | Metasin—An Intra-Operative RT-qPCR Assay to Detect Metastatic Breast Cancer in Sentinel Lymph Nodes |
title_sort | metasin—an intra-operative rt-qpcr assay to detect metastatic breast cancer in sentinel lymph nodes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742166/ https://www.ncbi.nlm.nih.gov/pubmed/23797656 http://dx.doi.org/10.3390/ijms140712931 |
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