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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2016-03

AUTHORS

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

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. More... »

PAGES

313-319

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00428-015-1892-7

DOI

http://dx.doi.org/10.1007/s00428-015-1892-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1049377652

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26637197


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