Prognostic implication of molecular subtypes and response to neoadjuvant chemotherapy in 760 gastric carcinomas: role of Epstein–Barr virus infection and high‐ and low‐microsatellite instability
Abstract Epstein–Barr virus positivity (EBV(+)) and high‐microsatellite instability (MSI‐H) have been identified as molecular subgroups in gastric carcinoma. The aim of our study was to determine the prognostic and predictive relevance of these subgroups in the context of platinum/5‐fluorouracil (5‐...
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Language: | English |
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Wiley
2019-10-01
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Series: | The Journal of Pathology: Clinical Research |
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Online Access: | https://doi.org/10.1002/cjp2.137 |
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doaj-1459b21410b843e08844499d9774926e |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Meike Kohlruss Bianca Grosser Marie Krenauer Julia Slotta‐Huspenina Moritz Jesinghaus Susanne Blank Alexander Novotny Magdalena Reiche Thomas Schmidt Liridona Ismani Alexander Hapfelmeier Daniel Mathias Petra Meyer Matthias M Gaida Lukas Bauer Katja Ott Wilko Weichert Gisela Keller |
spellingShingle |
Meike Kohlruss Bianca Grosser Marie Krenauer Julia Slotta‐Huspenina Moritz Jesinghaus Susanne Blank Alexander Novotny Magdalena Reiche Thomas Schmidt Liridona Ismani Alexander Hapfelmeier Daniel Mathias Petra Meyer Matthias M Gaida Lukas Bauer Katja Ott Wilko Weichert Gisela Keller Prognostic implication of molecular subtypes and response to neoadjuvant chemotherapy in 760 gastric carcinomas: role of Epstein–Barr virus infection and high‐ and low‐microsatellite instability The Journal of Pathology: Clinical Research microsatellite instability Epstein–Barr virus adenocarcinoma gastric gastro‐oesophageal junction outcome |
author_facet |
Meike Kohlruss Bianca Grosser Marie Krenauer Julia Slotta‐Huspenina Moritz Jesinghaus Susanne Blank Alexander Novotny Magdalena Reiche Thomas Schmidt Liridona Ismani Alexander Hapfelmeier Daniel Mathias Petra Meyer Matthias M Gaida Lukas Bauer Katja Ott Wilko Weichert Gisela Keller |
author_sort |
Meike Kohlruss |
title |
Prognostic implication of molecular subtypes and response to neoadjuvant chemotherapy in 760 gastric carcinomas: role of Epstein–Barr virus infection and high‐ and low‐microsatellite instability |
title_short |
Prognostic implication of molecular subtypes and response to neoadjuvant chemotherapy in 760 gastric carcinomas: role of Epstein–Barr virus infection and high‐ and low‐microsatellite instability |
title_full |
Prognostic implication of molecular subtypes and response to neoadjuvant chemotherapy in 760 gastric carcinomas: role of Epstein–Barr virus infection and high‐ and low‐microsatellite instability |
title_fullStr |
Prognostic implication of molecular subtypes and response to neoadjuvant chemotherapy in 760 gastric carcinomas: role of Epstein–Barr virus infection and high‐ and low‐microsatellite instability |
title_full_unstemmed |
Prognostic implication of molecular subtypes and response to neoadjuvant chemotherapy in 760 gastric carcinomas: role of Epstein–Barr virus infection and high‐ and low‐microsatellite instability |
title_sort |
prognostic implication of molecular subtypes and response to neoadjuvant chemotherapy in 760 gastric carcinomas: role of epstein–barr virus infection and high‐ and low‐microsatellite instability |
publisher |
Wiley |
series |
The Journal of Pathology: Clinical Research |
issn |
2056-4538 |
publishDate |
2019-10-01 |
description |
Abstract Epstein–Barr virus positivity (EBV(+)) and high‐microsatellite instability (MSI‐H) have been identified as molecular subgroups in gastric carcinoma. The aim of our study was to determine the prognostic and predictive relevance of these subgroups in the context of platinum/5‐fluorouracil (5‐FU) based preoperative chemotherapy (CTx). Additionally, we investigated the clinical relevance of the low‐MSI (MSI‐L) phenotype. We analysed 760 adenocarcinomas of the stomach or the gastro‐oesophageal junction encompassing 143 biopsies before CTx and 617 resected tumours (291 without and 326 after CTx). EBV was determined by PCR and in situ hybridisation for selected cases. MSI was analysed by PCR using five microsatellite markers and classified as MSI‐H and MSI‐L. Frequencies of EBV(+), MSI‐H and MSI‐L in the biopsies before CTx were 4.2, 10.5 and 4.9% respectively. EBV(+) or MSI‐H did not correlate with response, but MSI‐L was associated with better response (p = 0.011). In the resected tumours, frequencies of EBV(+), MSI‐H and MSI‐L were 3.9, 9.6 and 4.5% respectively. Overall survival (OS) was significantly different in the non‐CTx group (p = 0.014). Patients with EBV(+) tumours showed the best OS, followed by MSI‐H. MSI‐L was significantly associated with worse OS (hazard ratio [HR], 2.21; 95% confidence interval [CI], 1.21–4.04, p = 0.01). In the resected tumours after CTx, MSI‐H was also associated with increased OS (HR, 0.54; 95% CI, 0.26–1.09, p = 0.085). In multivariable analysis, molecular classification was an independent prognostic factor in the completely resected (R0) non‐CTx group (p = 0.035). In conclusion, MSI‐H and EBV(+) are not predictive of response to neoadjuvant platinum/5‐FU based CTx, but they are indicative of a good prognosis. In particular, MSI‐H indicates a favourable prognosis irrespective of treatment with CTx. MSI‐L predicts good response to CTx and its negative prognostic effect for patients treated with surgery alone suggests that MSI‐L might help to identify patients with potentially high‐benefit from preoperative CTx. |
topic |
microsatellite instability Epstein–Barr virus adenocarcinoma gastric gastro‐oesophageal junction outcome |
url |
https://doi.org/10.1002/cjp2.137 |
work_keys_str_mv |
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doaj-1459b21410b843e08844499d9774926e2020-11-25T01:32:12ZengWileyThe Journal of Pathology: Clinical Research2056-45382019-10-015422723910.1002/cjp2.137Prognostic implication of molecular subtypes and response to neoadjuvant chemotherapy in 760 gastric carcinomas: role of Epstein–Barr virus infection and high‐ and low‐microsatellite instabilityMeike Kohlruss0Bianca Grosser1Marie Krenauer2Julia Slotta‐Huspenina3Moritz Jesinghaus4Susanne Blank5Alexander Novotny6Magdalena Reiche7Thomas Schmidt8Liridona Ismani9Alexander Hapfelmeier10Daniel Mathias11Petra Meyer12Matthias M Gaida13Lukas Bauer14Katja Ott15Wilko Weichert16Gisela Keller17Institute of Pathology Technical University of Munich Munich GermanyInstitute of Pathology Technical University of Munich Munich GermanyInstitute of Pathology Technical University of Munich Munich GermanyInstitute of Pathology Technical University of Munich Munich GermanyInstitute of Pathology Technical University of Munich Munich GermanyDepartment of Surgery University of Heidelberg Heidelberg GermanyDepartment of Surgery Technical University of Munich Munich GermanyInstitute of Pathology Technical University of Munich Munich GermanyDepartment of Surgery University of Heidelberg Heidelberg GermanyInstitute of Pathology Technical University of Munich Munich GermanyInstitute of Medical Informatics, Statistics and Epidemiology Technical University of Munich Munich GermanyInstitute of Pathology Technical University of Munich Munich GermanyInstitute of Pathology Technical University of Munich Munich GermanyInstitute of Pathology University of Heidelberg Heidelberg GermanyInstitute of Pathology Technical University of Munich Munich GermanyDepartment of Surgery Klinikum Rosenheim Rosenheim GermanyInstitute of Pathology Technical University of Munich Munich GermanyInstitute of Pathology Technical University of Munich Munich GermanyAbstract Epstein–Barr virus positivity (EBV(+)) and high‐microsatellite instability (MSI‐H) have been identified as molecular subgroups in gastric carcinoma. The aim of our study was to determine the prognostic and predictive relevance of these subgroups in the context of platinum/5‐fluorouracil (5‐FU) based preoperative chemotherapy (CTx). Additionally, we investigated the clinical relevance of the low‐MSI (MSI‐L) phenotype. We analysed 760 adenocarcinomas of the stomach or the gastro‐oesophageal junction encompassing 143 biopsies before CTx and 617 resected tumours (291 without and 326 after CTx). EBV was determined by PCR and in situ hybridisation for selected cases. MSI was analysed by PCR using five microsatellite markers and classified as MSI‐H and MSI‐L. Frequencies of EBV(+), MSI‐H and MSI‐L in the biopsies before CTx were 4.2, 10.5 and 4.9% respectively. EBV(+) or MSI‐H did not correlate with response, but MSI‐L was associated with better response (p = 0.011). In the resected tumours, frequencies of EBV(+), MSI‐H and MSI‐L were 3.9, 9.6 and 4.5% respectively. Overall survival (OS) was significantly different in the non‐CTx group (p = 0.014). Patients with EBV(+) tumours showed the best OS, followed by MSI‐H. MSI‐L was significantly associated with worse OS (hazard ratio [HR], 2.21; 95% confidence interval [CI], 1.21–4.04, p = 0.01). In the resected tumours after CTx, MSI‐H was also associated with increased OS (HR, 0.54; 95% CI, 0.26–1.09, p = 0.085). In multivariable analysis, molecular classification was an independent prognostic factor in the completely resected (R0) non‐CTx group (p = 0.035). In conclusion, MSI‐H and EBV(+) are not predictive of response to neoadjuvant platinum/5‐FU based CTx, but they are indicative of a good prognosis. In particular, MSI‐H indicates a favourable prognosis irrespective of treatment with CTx. MSI‐L predicts good response to CTx and its negative prognostic effect for patients treated with surgery alone suggests that MSI‐L might help to identify patients with potentially high‐benefit from preoperative CTx.https://doi.org/10.1002/cjp2.137microsatellite instabilityEpstein–Barr virusadenocarcinomagastricgastro‐oesophageal junctionoutcome |