Occurrence of High Microsatellite-Instability/Mismatch Repair Deficiency in Nearly 2,000 Human Adenocarcinomas of the Gastrointestinal Tract, Pancreas, and Bile Ducts: A Study From a Large German Comprehensive Cancer Center
IntroductionKnowledge of the high microsatellite-instability (MSI-H)/mismatch repair deficiency (MMRd) status is of increasing interest for personalized neoadjuvant or adjuvant therapy planning. Only a few studies are available on MSI-H distribution in the Northern European Caucasian patient populat...
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Frontiers Media S.A.
2021-07-01
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Series: | Frontiers in Oncology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.569475/full |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alexander Quaas Jan Rehkaemper Josef Rueschoff Aylin Pamuk Thomas Zander Axel Hillmer Janna Siemanowski Jana Wittig Reinhard Buettner Patrick Plum Felix Popp Florian Gebauer Christiane Josephine Bruns Heike Loeser Hakan Alakus Birgid Schoemig-Markiefka |
spellingShingle |
Alexander Quaas Jan Rehkaemper Josef Rueschoff Aylin Pamuk Thomas Zander Axel Hillmer Janna Siemanowski Jana Wittig Reinhard Buettner Patrick Plum Felix Popp Florian Gebauer Christiane Josephine Bruns Heike Loeser Hakan Alakus Birgid Schoemig-Markiefka Occurrence of High Microsatellite-Instability/Mismatch Repair Deficiency in Nearly 2,000 Human Adenocarcinomas of the Gastrointestinal Tract, Pancreas, and Bile Ducts: A Study From a Large German Comprehensive Cancer Center Frontiers in Oncology Union for International Cancer Control (UICC) stage 4 esophageal adenocarcinoma gastric carcinoma high microsatellite-instability (MSI-H) microsatellite-instability |
author_facet |
Alexander Quaas Jan Rehkaemper Josef Rueschoff Aylin Pamuk Thomas Zander Axel Hillmer Janna Siemanowski Jana Wittig Reinhard Buettner Patrick Plum Felix Popp Florian Gebauer Christiane Josephine Bruns Heike Loeser Hakan Alakus Birgid Schoemig-Markiefka |
author_sort |
Alexander Quaas |
title |
Occurrence of High Microsatellite-Instability/Mismatch Repair Deficiency in Nearly 2,000 Human Adenocarcinomas of the Gastrointestinal Tract, Pancreas, and Bile Ducts: A Study From a Large German Comprehensive Cancer Center |
title_short |
Occurrence of High Microsatellite-Instability/Mismatch Repair Deficiency in Nearly 2,000 Human Adenocarcinomas of the Gastrointestinal Tract, Pancreas, and Bile Ducts: A Study From a Large German Comprehensive Cancer Center |
title_full |
Occurrence of High Microsatellite-Instability/Mismatch Repair Deficiency in Nearly 2,000 Human Adenocarcinomas of the Gastrointestinal Tract, Pancreas, and Bile Ducts: A Study From a Large German Comprehensive Cancer Center |
title_fullStr |
Occurrence of High Microsatellite-Instability/Mismatch Repair Deficiency in Nearly 2,000 Human Adenocarcinomas of the Gastrointestinal Tract, Pancreas, and Bile Ducts: A Study From a Large German Comprehensive Cancer Center |
title_full_unstemmed |
Occurrence of High Microsatellite-Instability/Mismatch Repair Deficiency in Nearly 2,000 Human Adenocarcinomas of the Gastrointestinal Tract, Pancreas, and Bile Ducts: A Study From a Large German Comprehensive Cancer Center |
title_sort |
occurrence of high microsatellite-instability/mismatch repair deficiency in nearly 2,000 human adenocarcinomas of the gastrointestinal tract, pancreas, and bile ducts: a study from a large german comprehensive cancer center |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-07-01 |
description |
IntroductionKnowledge of the high microsatellite-instability (MSI-H)/mismatch repair deficiency (MMRd) status is of increasing interest for personalized neoadjuvant or adjuvant therapy planning. Only a few studies are available on MSI-H distribution in the Northern European Caucasian patient population. In this study, we focused on a large cohort of tumors of the upper gastrointestinal tract.Materials and MethodsSurgical material from a total of 1,965 patients was analyzed for MSI-H/MMRd status (including 1,267 carcinomas of the esophagus or stomach). All tumors were analyzed with an internationally recommended immunohistochemical panel consisting of four antibodies (MLH1, MSH2, PMS2, and MSH6). The results were molecularly objectified.ResultsAdenocarcinomas with MSI-H/MMRd were detected with the following distribution: esophagus (1.4%), stomach (8.3%), small intestine (18.2%), large intestine (8.5%), intrahepatic bile ducts (1.9%), and pancreas (0%). In case of gastric tumors with MSI-H/MMRd, neoadjuvant therapy did not influence the prognosis of patients (p = 0.94). Within all tumor entities with MSI-H/MMRd, patients with a UICC stage 4 were also represented. In this advanced stage, 11.7% of patients with MSS tumors were diagnosed compared to 0.5% of patients with MSI-H tumors relative to the entire tumor collective.DiscussionIn this study, the proportion of MSI-H/MMRd tumors in the stomach is smaller than would have been expected in knowledge of the data published by TCGA or AGRC. Negative prognostic effects regarding MSI-H status and neoadjuvant therapy as described by the MAGIC study group were not seen in our cohort. The extent to which the MSI-H/MMRd status should be known for neoadjuvant therapy planning must be clarified in prospective studies in the future. At present, there is no convincing data to dispense the neoadjuvant therapy for gastric carcinoma. Due to the very convincing, positive data regarding the response rates of MSI-H tumors to treatment with PD1/PD-L1 inhibitors, every metastatic carcinoma of the gastrointestinal tract should be tested for its MSI-H status. |
topic |
Union for International Cancer Control (UICC) stage 4 esophageal adenocarcinoma gastric carcinoma high microsatellite-instability (MSI-H) microsatellite-instability |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.569475/full |
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doaj-0c40ecf5883e4e8b83433c043aedb1c02021-07-23T13:03:56ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-07-011110.3389/fonc.2021.569475569475Occurrence of High Microsatellite-Instability/Mismatch Repair Deficiency in Nearly 2,000 Human Adenocarcinomas of the Gastrointestinal Tract, Pancreas, and Bile Ducts: A Study From a Large German Comprehensive Cancer CenterAlexander Quaas0Jan Rehkaemper1Josef Rueschoff2Aylin Pamuk3Thomas Zander4Axel Hillmer5Janna Siemanowski6Jana Wittig7Reinhard Buettner8Patrick Plum9Felix Popp10Florian Gebauer11Christiane Josephine Bruns12Heike Loeser13Hakan Alakus14Birgid Schoemig-Markiefka15Institute of Pathology, University Hospital Cologne, Cologne, GermanyInstitute of Pathology, University Hospital Cologne, Cologne, GermanyInstitute of Pathology, Nordhessen and Targos Molecular Pathology GmbH, Kassel, GermanyDepartment of General, Visceral and Cancer Surgery, University Hospital Cologne, Cologne, GermanyDepartment of Internal Medicine I, University Hospital Cologne, Cologne, GermanyInstitute of Pathology, University Hospital Cologne, Cologne, GermanyInstitute of Pathology, University Hospital Cologne, Cologne, GermanyInstitute of Pathology, University Hospital Cologne, Cologne, GermanyInstitute of Pathology, University Hospital Cologne, Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University Hospital Cologne, Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University Hospital Cologne, Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University Hospital Cologne, Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University Hospital Cologne, Cologne, GermanyInstitute of Pathology, University Hospital Cologne, Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University Hospital Cologne, Cologne, GermanyInstitute of Pathology, University Hospital Cologne, Cologne, GermanyIntroductionKnowledge of the high microsatellite-instability (MSI-H)/mismatch repair deficiency (MMRd) status is of increasing interest for personalized neoadjuvant or adjuvant therapy planning. Only a few studies are available on MSI-H distribution in the Northern European Caucasian patient population. In this study, we focused on a large cohort of tumors of the upper gastrointestinal tract.Materials and MethodsSurgical material from a total of 1,965 patients was analyzed for MSI-H/MMRd status (including 1,267 carcinomas of the esophagus or stomach). All tumors were analyzed with an internationally recommended immunohistochemical panel consisting of four antibodies (MLH1, MSH2, PMS2, and MSH6). The results were molecularly objectified.ResultsAdenocarcinomas with MSI-H/MMRd were detected with the following distribution: esophagus (1.4%), stomach (8.3%), small intestine (18.2%), large intestine (8.5%), intrahepatic bile ducts (1.9%), and pancreas (0%). In case of gastric tumors with MSI-H/MMRd, neoadjuvant therapy did not influence the prognosis of patients (p = 0.94). Within all tumor entities with MSI-H/MMRd, patients with a UICC stage 4 were also represented. In this advanced stage, 11.7% of patients with MSS tumors were diagnosed compared to 0.5% of patients with MSI-H tumors relative to the entire tumor collective.DiscussionIn this study, the proportion of MSI-H/MMRd tumors in the stomach is smaller than would have been expected in knowledge of the data published by TCGA or AGRC. Negative prognostic effects regarding MSI-H status and neoadjuvant therapy as described by the MAGIC study group were not seen in our cohort. The extent to which the MSI-H/MMRd status should be known for neoadjuvant therapy planning must be clarified in prospective studies in the future. At present, there is no convincing data to dispense the neoadjuvant therapy for gastric carcinoma. Due to the very convincing, positive data regarding the response rates of MSI-H tumors to treatment with PD1/PD-L1 inhibitors, every metastatic carcinoma of the gastrointestinal tract should be tested for its MSI-H status.https://www.frontiersin.org/articles/10.3389/fonc.2021.569475/fullUnion for International Cancer Control (UICC) stage 4esophageal adenocarcinomagastric carcinomahigh microsatellite-instability (MSI-H)microsatellite-instability |