Microsatellite instability in pulmonary adenocarcinomas

• Verfasst von: Warth, Arne [VerfasserIn]
• Verfasst von: Körner, Sandrina [VerfasserIn]
• Verfasst von: Penzel, Roland [VerfasserIn]
• Verfasst von: Muley, Thomas [VerfasserIn]
• Verfasst von: Dienemann, Hendrik [VerfasserIn]
• Verfasst von: Schirmacher, Peter [VerfasserIn]
• Verfasst von: Knebel Doeberitz, Magnus von [VerfasserIn]
• Verfasst von: Weichert, Wilko [VerfasserIn]
• Verfasst von: Kloor, Matthias [VerfasserIn]
• Titel: Microsatellite instability in pulmonary adenocarcinomas
• Titelzusatz: a comprehensive study of 480 cases
• Verf.angabe: Arne Warth, Sandrina Körner, Roland Penzel, Thomas Muley, Hendrik Dienemann, Peter Schirmacher, Magnus von Knebel-Doeberitz, Wilko Weichert, Matthias Kloor
• Jahr: 2016
• Umfang: 7 S.
• Fussnoten: Published online: 4 December 2015 ; Gesehen am 28.02.2020
• Titel Quelle: Enthalten in: Virchows Archiv
• Ort Quelle: Berlin : Springer, 1847
• Jahr Quelle: 2016
• Band/Heft Quelle: 468(2016), 3, Seite 313-319
• ISSN Quelle: 1432-2307
• DOI: doi:10.1007/s00428-015-1892-7
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 169126704X

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.