Universität zu Köln

Herz, Anna-Lina, Wisser, Sarah, Kohlruss, Meike, Slotta-Huspenina, Julia, Jesinghaus, Moritz ORCID: 0000-0002-0018-5661, Grosser, Bianca, Steiger, Katja ORCID: 0000-0002-7269-5433, Novotny, Alexander, Hapfelmeier, Alexander, Schmidt, Thomas, Gaida, Matthias M., Weichert, Wilko and Keller, Gisela (2022). Elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in gastric cancer: a distinct microsatellite instability type with potential clinical impact? J. Pathol. Clin. Res., 8 (3). S. 233 - 245. HOBOKEN: WILEY. ISSN 2056-4538

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Abstract

We investigated the clinical impact of elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in the context of neoadjuvant chemotherapy (CTx) in gastric/gastro-oesophageal adenocarcinomas. We analysed 583 resected tumours (272 without and 311 after CTx) and 142 tumour biopsies before CTx. If at least two or three of the five tetranucleotide repeat markers tested showed instability, the tumours were defined as EMAST (2+) or EMAST (3+), respectively. Expression of mismatch repair proteins including MSH3 was analysed using immunohistochemistry. Microsatellite instability (MSI) and Epstein-Barr virus (EBV) positivity were determined using standard assays. EMAST (2+) and (3+) were detected in 17.8 and 11.5% of the tumours, respectively. The frequency of EMAST (2+) or (3+) in MSI-high (MSI-H) tumours was 96.2 or 92.5%, respectively, demonstrating a high overlap with this molecular subtype, and the association of EMAST and MSI status was significant (each overall p < 0.001). EMAST (2+ or 3+) alone in MSI-H and EBV-negative tumours demonstrated only a statistically significant association of EMAST (2+) positivity and negative lymph node status (42.3% in EMAST (2+) and 28.8% in EMAST negative, p = 0.045). EMAST alone by neither definition was significantly associated with overall survival (OS) of the patients. The median OS for EMAST (2+) patients was 40.0 months (95% confidence interval [CI] 16.4-63.6) compared with 38.7 months (95% CI 26.3-51.1) for the EMAST-negative group (p = 0.880). The median OS for EMAST (3+) patients was 46.7 months (95% CI 18.2-75.2) and 38.7 months (95% CI 26.2-51.2) for the negative group (p = 0.879). No statistically significant association with response to neoadjuvant CTx was observed (p = 0.992 and p = 0.433 for EMAST (2+) and (3+), respectively). In conclusion, our results demonstrate a nearly complete intersection between MSI-H and EMAST and they indicate that EMAST alone is not a distinct instability type associated with noticeable clinico-pathological characteristics of gastric carcinoma patients.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Herz, Anna-Lina UNSPECIFIED UNSPECIFIED UNSPECIFIED Wisser, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Kohlruss, Meike UNSPECIFIED UNSPECIFIED UNSPECIFIED Slotta-Huspenina, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Jesinghaus, Moritz UNSPECIFIED orcid.org/0000-0002-0018-5661 UNSPECIFIED Grosser, Bianca UNSPECIFIED UNSPECIFIED UNSPECIFIED Steiger, Katja UNSPECIFIED orcid.org/0000-0002-7269-5433 UNSPECIFIED Novotny, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Hapfelmeier, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Gaida, Matthias M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Weichert, Wilko UNSPECIFIED UNSPECIFIED UNSPECIFIED Keller, Gisela UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-687051
DOI:	10.1002/cjp2.257
Journal or Publication Title:	J. Pathol. Clin. Res.
Volume:	8
Number:	3
Page Range:	S. 233 - 245
Date:	2022
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	2056-4538
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COLORECTAL-CANCER; NEOADJUVANT CHEMOTHERAPY; IMMUNOHISTOCHEMISTRY; SURVIVAL; REGRESSION Multiple languages Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68705