KRAS Mutation is Predictive of Outcome in Patients with Pulmonary Sarcomatoid Carcinoma

Abstract

Pulmonary Sarcomatoid Carcinoma (PSC) is a poorly-differentiated non-small cell lung carcinoma (NSCLC) with aggressive behavior. This study aimed to evaluate the prognostic clinicopathologic and genetic characteristics of PSCs. Fifty-three cases of surgically treated PSCs were selected, of which 23 were subjected to mutation and copy number variation analysis using 50-gene Ion AmpliSeq Cancer Panel. Majority of the patients were male (32/53, 60.3%) and smoker (51/53, 96.2%). Overall, 25 (47.1%) patients died within 2 to 105 months (mean 22.7 months, median 15 months) after diagnosis, and 28 were alive as of 3 to 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 over 70 years (p=0.008) and tumor size ≥ 4.0 cm (p= 0.02) were strongly associated with worse outcome. TP53 (17/23, 74.0%) and KRAS codon 12/13 mutations (10/23, 43.4%) were the most common genetic alterations. Potentially actionable variants were identified including ATM (4/23, 17.3%), MET, FBXW7 and EGFR (2/23, 8.7%), AKT1, KIT, PDGFRA, HRAS, JAK3, and SMAD4 (1/23, 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 (3/23, 13%) and ATM (2/23, 8.7%). Copy number gains were seen in EGFR (2/23, 13.0%), and in one (4.3%) of each PIK3CA, KRAS, MET, and STK11. Potentially targetable mutations can be identified in a subset of PSC although most tumors harbor currently untargetable prognostically adverse TP53 and KRAS mutations.

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