MET exon 14 splice site mutation, protein expression, and amplification in pulmonary sarcomatoid carcinoma: A multi-center study from China.

e20595 Background: MET exon 14 splice site mutation (MET exon 14Δ) was identified as a potential driver mutation in non-small cell lung cancer (NSCLC). Previously, several small sample size studies have revealed a higher frequency in pulmonary sarcomatoid carcinoma (PSC) than other types of NSCLC. In order to reveal the accurate frequency of MET gene alterations in Chinese PSCs, we comprehensively studied the frequency and the relationship among MET exon 14Δ, protein expression and amplification in a large cohort of PSCs. Methods: MET exon 14Δ, protein expression and amplification were detected in 148 surgically resected PSC samples from multiple medical centers by using Sanger sequencing, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively. Results: MET exon 14Δ was identified in 9 (6.1%) of 148 cases. Six were pleomorphic carcinoma, two were spindle cell carcinoma and one was carcinosarcoma. MET exon 14Δ was more common in pleomorphic carcinoma compared with other subtypes of PSCs (p = 0.01, X2 test) and have an obvious tendency to occur in elder patients. MET protein overexpression was detected in 16.2% (24/148) of PSCs, and was found significantly associated with MET exon 14Δ (p = 0.045). MET FISH positive was detected in 15.5% (23/148), and 6 (4.1%) of them were confirmed as gene amplifications. MET FISH positivity (P < 0.001, X2 test) and amplification (P < 0.001, X2 test) were significantly associated with the IHC positive. No significant relationship between MET exon 14Δ and amplification was found. Conclusions: Chinese PSC has high incidence of METexon 14Δ and amplication. MET inhibition may benefit this specific subgroup of patients.