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01-03-2016 | Original Article

Microsatellite instability in pulmonary adenocarcinomas: a comprehensive study of 480 cases

Authors: Arne Warth, Sandrina Körner, Roland Penzel, Thomas Muley, Hendrik Dienemann, Peter Schirmacher, Magnus von Knebel-Doeberitz, Wilko Weichert, Matthias Kloor

Published in: Virchows Archiv | Issue 3/2016

Abstract

A major molecular pathway of genetic instability in cancer is DNA mismatch repair deficiency, leading to accumulation of numerous mutations at repetitive DNA sequence stretches (microsatellites), known as high-level microsatellite instability (MSI-H). In colorectal cancer, MSI-H tumors show a clinical behavior different from microsatellite-stable (MSS) tumors. Data about the prevalence of MSI among non-small cell lung cancer (NSCLC) are conflicting, and clinical relevance of MSI is largely unknown. We analyzed a series of 480 pulmonary adenocarcinomas (ADC) for MSI using a sensitive mononucleotide marker panel (BAT25, BAT26, and CAT25). Positive cases were further analyzed by immunohistochemical staining for DNA mismatch repair proteins. Results were correlated with clinicopathological variables. MSI-H was detected in 4/480 (0.8 %) cases. In none of these, a background of Lynch syndrome was found. Three of the patients developed a metachronous carcinoma (esophagus, pancreas, and kidney). All MSI-H cases were stage I and occurred in smokers/ex-smokers. Mutations were found in EGFR (n = 2), KRAS (n = 1), or BRAF (n = 1). MSI-H neoplasms had a higher proliferative activity (38.7 %) than MSS neoplasms (28.3 %). Mean overall survival for MSS and MSI-H cases was 64.8 (CI 60.4–69.1) and 47.1 (CI 21–73.2) months, respectively. When specific mononucleotide marker panels are applied, the MSI-H phenotype is rare and predominantly found in early stage ADC of smokers. However, the frequency of MSI-H is in the range of other relevant molecular alterations. In the era of precision therapy, associations with distinct clinicopathological variables merit further investigation.

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Title: Microsatellite instability in pulmonary adenocarcinomas: a comprehensive study of 480 cases
Authors: Arne Warth
Sandrina Körner
Roland Penzel
Thomas Muley
Hendrik Dienemann
Peter Schirmacher
Magnus von Knebel-Doeberitz
Wilko Weichert
Matthias Kloor
Publication date: 01-03-2016
Publisher: Springer Berlin Heidelberg
Published in: Virchows Archiv / Issue 3/2016
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-015-1892-7

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Microsatellite instability in pulmonary adenocarcinomas: a comprehensive study of 480 cases

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