KRAS KRAS KRAS mutation is predictive of outcome in patients with pulmonary sarcomatoid carcinoma

摘要

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 PSC s. Methods and results Fifty‐three cases of surgically treated PSC s 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. TP 53 (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 , FBXW 7 and EGFR (two of 23, 8.7%), AKT 1 , KIT , PDGFRA , HRAS , JAK 3 and SMAD 4 (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 RB 1 (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 PIK 3 CA , KRAS , MET and STK 11 . Conclusions Potentially targetable mutations can be identified in a subset of PSC , although most tumours harbour currently untargetable prognostically adverse TP 53 and KRAS mutations.