Universität zu Köln

Quaas, Alexander, Rehkaemper, Jan, Rueschoff, Josef, Pamuk, Aylin, Zander, Thomas, Hillmer, Axel, Siemanowski, Janna, Wittig, Jana, Buettner, Reinhard, Plum, Patrick, Popp, Felix, Gebauer, Florian, Bruns, Christiane Josephine, Loeser, Heike, Alakus, Hakan and Schoemig-Markiefka, Birgid (2021). 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. Front. Oncol., 11. LAUSANNE: FRONTIERS MEDIA SA. ISSN 2234-943X

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Abstract

Introduction: Knowledge 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 Methods: Surgical 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. Results: Adenocarcinomas 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. Discussion: In 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Rehkaemper, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Rueschoff, Josef UNSPECIFIED UNSPECIFIED UNSPECIFIED Pamuk, Aylin UNSPECIFIED UNSPECIFIED UNSPECIFIED Zander, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Hillmer, Axel UNSPECIFIED UNSPECIFIED UNSPECIFIED Siemanowski, Janna UNSPECIFIED UNSPECIFIED UNSPECIFIED Wittig, Jana UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Plum, Patrick UNSPECIFIED UNSPECIFIED UNSPECIFIED Popp, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Gebauer, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruns, Christiane Josephine UNSPECIFIED UNSPECIFIED UNSPECIFIED Loeser, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Alakus, Hakan UNSPECIFIED UNSPECIFIED UNSPECIFIED Schoemig-Markiefka, Birgid UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-574113
DOI:	10.3389/fonc.2021.569475
Journal or Publication Title:	Front. Oncol.
Volume:	11
Date:	2021
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	2234-943X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MISMATCH-REPAIR; COLORECTAL-CANCER; ESOPHAGEAL; PATHOGENESIS; TUMORS Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57411