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Title: KRAS mutation is predictive of outcome in patients with pulmonary sarcomatoid carcinoma
Authors: Mitra Mehrad
Somak Roy
William A. LaFramboise
Patti Petrosko
Caitlyn Miller
Pimpin Incharoen
Sanja Dacic
Vanderbilt University Medical Center
Mahidol University
University of Pittsburgh Medical Center
Keywords: Medicine
Issue Date: 1-Aug-2018
Citation: Histopathology. Vol.73, No.2 (2018), 207-214
Abstract: © 2018 John Wiley & Sons Ltd Aims: Pulmonary sarcomatoid carcinoma (PSC) is a poorly differentiated non-small-cell lung carcinoma (NSCLC) with aggressive behaviour. This study aimed to evaluate the prognostic clinicopathological and genetic characteristics of PSCs. Methods and results: Fifty-three cases of surgically treated PSCs were selected, 23 of which were subjected to mutation and copy number variation analysis using the 50-gene Ion AmpliSeq Cancer Panel. The majority of the patients were male (32 of 53, 60.3%) and smokers (51 of 53, 96.2%). Overall, 25 (47.1%) patients died within 2–105 months (mean = 22.7 months, median = 15 months) after diagnosis, and 28 were alive 3–141 months (mean = 38.7 months, median = 21.5 months) after diagnosis. Five-year overall survival was 12.5%. KRAS codon 12/13 mutation in adenocarcinomas (P = 0.01), age more than 70 years (P = 0.008) and tumour size ≥4.0 cm (P = 0.02) were associated strongly with worse outcome. TP53 (17 of 23, 74.0%) and KRAS codon 12 of 13 mutations (10 of 23, 43.4%) were the most common genetic alterations. Potentially actionable variants were identified including ATM (four of 23, 17.3%), MET, FBXW7 and EGFR (two of 23, 8.7%), AKT1, KIT, PDGFRA, HRAS, JAK3 and SMAD4 (one of 23, 4.3%). MET exon 14 skipping and missense mutations were identified in two (11.1%) cases with adenocarcinoma histology. Copy number analysis showed loss of RB1 (three of 23, 13%) and ATM (two of 23, 8.7%). Copy number gains were seen in EGFR (two of 23, 13.0%) and in one (4.3%) of each PIK3CA, KRAS, MET and STK11. Conclusions: Potentially targetable mutations can be identified in a subset of PSC, although most tumours harbour currently untargetable prognostically adverse TP53 and KRAS mutations.
ISSN: 13652559
Appears in Collections:Scopus 2018

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