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YKL-40/c-Met Expression in Rectal Cancer Biopsies Predicts Tumor Regression following Neoadjuvant Chemoradiotherapy: A Multi-Institutional Study

BACKGROUND: Neoadjuvant chemo-radiotherapy (CRT) followed by surgical resection is the standard treatment for locally advanced rectal cancer, although complete tumor pathological regression is achieved in only up to 30% of cases. A clinicopathological and molecular predictive stratification of patie...

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Autores principales: Senetta, Rebecca, Duregon, Eleonora, Sonetto, Cristina, Spadi, Rossella, Mistrangelo, Massimiliano, Racca, Patrizia, Chiusa, Luigi, Munoz, Fernando H., Ricardi, Umberto, Arezzo, Alberto, Cassenti, Adele, Castellano, Isabella, Papotti, Mauro, Morino, Mario, Risio, Mauro, Cassoni, Paola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398550/
https://www.ncbi.nlm.nih.gov/pubmed/25875173
http://dx.doi.org/10.1371/journal.pone.0123759
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author Senetta, Rebecca
Duregon, Eleonora
Sonetto, Cristina
Spadi, Rossella
Mistrangelo, Massimiliano
Racca, Patrizia
Chiusa, Luigi
Munoz, Fernando H.
Ricardi, Umberto
Arezzo, Alberto
Cassenti, Adele
Castellano, Isabella
Papotti, Mauro
Morino, Mario
Risio, Mauro
Cassoni, Paola
author_facet Senetta, Rebecca
Duregon, Eleonora
Sonetto, Cristina
Spadi, Rossella
Mistrangelo, Massimiliano
Racca, Patrizia
Chiusa, Luigi
Munoz, Fernando H.
Ricardi, Umberto
Arezzo, Alberto
Cassenti, Adele
Castellano, Isabella
Papotti, Mauro
Morino, Mario
Risio, Mauro
Cassoni, Paola
author_sort Senetta, Rebecca
collection PubMed
description BACKGROUND: Neoadjuvant chemo-radiotherapy (CRT) followed by surgical resection is the standard treatment for locally advanced rectal cancer, although complete tumor pathological regression is achieved in only up to 30% of cases. A clinicopathological and molecular predictive stratification of patients with advanced rectal cancer is still lacking. Here, c-Met and YKL-40 have been studied as putative predictors of CRT response in rectal cancer, due to their reported involvement in chemoradioresistance in various solid tumors. MATERIAL AND METHODS: A multicentric study was designed to assess the role of c-Met and YKL-40 expression in predicting chemoradioresistance and to correlate clinical and pathological features with CRT response. Immunohistochemistry and fluorescent in situ hybridization for c-Met were performed on 81 rectal cancer biopsies from patients with locally advanced rectal adenocarcinoma. All patients underwent standard (50.4 gy in 28 fractions + concurrent capecitabine 825 mg/m(2)) neoadjuvant CRT or the XELOXART protocol. CRT response was documented on surgical resection specimens and recorded as tumor regression grade (TRG) according to the Mandard criteria. RESULTS: A significant correlation between c-Met and YKL-40 expression was observed (R = 0.43). The expressions of c-Met and YKL-40 were both significantly associated with a lack of complete response (86% and 87% of c-Met and YKL-40 positive cases, p< 0.01 and p = 0.006, respectively). Thirty of the 32 biopsies co-expressing both markers had partial or absent tumor response (TRG 2-5), strengthening their positive predictive value (94%). The exclusive predictive role of YKL-40 and c-Met was confirmed using a multivariate analysis (p = 0.004 and p = 0.007 for YKL-40 and c-Met, respectively). TRG was the sole morphological parameter associated with poor outcome. CONCLUSION: c-Met and YKL-40 expression is a reliable predictor of partial/absent response to neoadjuvant CRT in rectal cancer. Targeted therapy protocols could take advantage of prior evaluations of c-MET and YKL-40 expression levels to increase therapeutic efficacy.
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spelling pubmed-43985502015-04-21 YKL-40/c-Met Expression in Rectal Cancer Biopsies Predicts Tumor Regression following Neoadjuvant Chemoradiotherapy: A Multi-Institutional Study Senetta, Rebecca Duregon, Eleonora Sonetto, Cristina Spadi, Rossella Mistrangelo, Massimiliano Racca, Patrizia Chiusa, Luigi Munoz, Fernando H. Ricardi, Umberto Arezzo, Alberto Cassenti, Adele Castellano, Isabella Papotti, Mauro Morino, Mario Risio, Mauro Cassoni, Paola PLoS One Research Article BACKGROUND: Neoadjuvant chemo-radiotherapy (CRT) followed by surgical resection is the standard treatment for locally advanced rectal cancer, although complete tumor pathological regression is achieved in only up to 30% of cases. A clinicopathological and molecular predictive stratification of patients with advanced rectal cancer is still lacking. Here, c-Met and YKL-40 have been studied as putative predictors of CRT response in rectal cancer, due to their reported involvement in chemoradioresistance in various solid tumors. MATERIAL AND METHODS: A multicentric study was designed to assess the role of c-Met and YKL-40 expression in predicting chemoradioresistance and to correlate clinical and pathological features with CRT response. Immunohistochemistry and fluorescent in situ hybridization for c-Met were performed on 81 rectal cancer biopsies from patients with locally advanced rectal adenocarcinoma. All patients underwent standard (50.4 gy in 28 fractions + concurrent capecitabine 825 mg/m(2)) neoadjuvant CRT or the XELOXART protocol. CRT response was documented on surgical resection specimens and recorded as tumor regression grade (TRG) according to the Mandard criteria. RESULTS: A significant correlation between c-Met and YKL-40 expression was observed (R = 0.43). The expressions of c-Met and YKL-40 were both significantly associated with a lack of complete response (86% and 87% of c-Met and YKL-40 positive cases, p< 0.01 and p = 0.006, respectively). Thirty of the 32 biopsies co-expressing both markers had partial or absent tumor response (TRG 2-5), strengthening their positive predictive value (94%). The exclusive predictive role of YKL-40 and c-Met was confirmed using a multivariate analysis (p = 0.004 and p = 0.007 for YKL-40 and c-Met, respectively). TRG was the sole morphological parameter associated with poor outcome. CONCLUSION: c-Met and YKL-40 expression is a reliable predictor of partial/absent response to neoadjuvant CRT in rectal cancer. Targeted therapy protocols could take advantage of prior evaluations of c-MET and YKL-40 expression levels to increase therapeutic efficacy. Public Library of Science 2015-04-15 /pmc/articles/PMC4398550/ /pubmed/25875173 http://dx.doi.org/10.1371/journal.pone.0123759 Text en © 2015 Senetta et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Senetta, Rebecca
Duregon, Eleonora
Sonetto, Cristina
Spadi, Rossella
Mistrangelo, Massimiliano
Racca, Patrizia
Chiusa, Luigi
Munoz, Fernando H.
Ricardi, Umberto
Arezzo, Alberto
Cassenti, Adele
Castellano, Isabella
Papotti, Mauro
Morino, Mario
Risio, Mauro
Cassoni, Paola
YKL-40/c-Met Expression in Rectal Cancer Biopsies Predicts Tumor Regression following Neoadjuvant Chemoradiotherapy: A Multi-Institutional Study
title YKL-40/c-Met Expression in Rectal Cancer Biopsies Predicts Tumor Regression following Neoadjuvant Chemoradiotherapy: A Multi-Institutional Study
title_full YKL-40/c-Met Expression in Rectal Cancer Biopsies Predicts Tumor Regression following Neoadjuvant Chemoradiotherapy: A Multi-Institutional Study
title_fullStr YKL-40/c-Met Expression in Rectal Cancer Biopsies Predicts Tumor Regression following Neoadjuvant Chemoradiotherapy: A Multi-Institutional Study
title_full_unstemmed YKL-40/c-Met Expression in Rectal Cancer Biopsies Predicts Tumor Regression following Neoadjuvant Chemoradiotherapy: A Multi-Institutional Study
title_short YKL-40/c-Met Expression in Rectal Cancer Biopsies Predicts Tumor Regression following Neoadjuvant Chemoradiotherapy: A Multi-Institutional Study
title_sort ykl-40/c-met expression in rectal cancer biopsies predicts tumor regression following neoadjuvant chemoradiotherapy: a multi-institutional study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398550/
https://www.ncbi.nlm.nih.gov/pubmed/25875173
http://dx.doi.org/10.1371/journal.pone.0123759
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