Publication: KRAS mutation is predictive of outcome in patients with pulmonary sarcomatoid carcinoma
Issued Date
2018-08-01
Resource Type
ISSN
13652559
03090167
03090167
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2-s2.0-85046544722
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Mahidol University
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SCOPUS
Bibliographic Citation
Histopathology. Vol.73, No.2 (2018), 207-214
Suggested Citation
Mitra Mehrad, Somak Roy, William A. LaFramboise, Patti Petrosko, Caitlyn Miller, Pimpin Incharoen, Sanja Dacic KRAS mutation is predictive of outcome in patients with pulmonary sarcomatoid carcinoma. Histopathology. Vol.73, No.2 (2018), 207-214. doi:10.1111/his.13505 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/46463
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Title
KRAS mutation is predictive of outcome in patients with pulmonary sarcomatoid carcinoma
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.