Comprehensive investigation of clinicopathologic features, oncogenic driver mutations and immunohistochemical markers in peripheral lung squamous cell carcinoma.

Abstract

Although the majority of lung squamous cell carcinomas (SQCC) arise in central airways, the prevalence of peripheral (p) SQCC is increasing. This study aimed to have a comprehensive investigation of clinicopathologic features, status of common driver mutations and immunophenotypes of p-SQCC compared to central (c) SQCC. A total of 261 p-SQCC were compared to 444 c-SQCC for clinicopathologic characteristics. Comprehensive mutational analysis of EGFR, KRAS, HER2, BRAF, PIK3CA, DDR2, AKT1, ALK, ROS1, RET and FGFRs were performed. TTF1, CK7, Napsin A and PE10 protein expression were analyzed through immunohistochemistry (IHC). TTF1, CK7, CK8, SPA and TP63 gene expression levels were measured by quantitative real-time PCR. Compared to c-SQCC, p-SQCC were associated with female (14.2% vs. 4.5%, P<0.001), never-smokers (22.6% vs. 13.3%, P=0.001), older age at diagnosis (64.9 vs. 59.5 years, P<0.001) and lower pathologic stage (P<0.001). The frequency of EGFR mutations was significantly higher in p-SQCC than c-SQCC (6.2% vs. 2.2%, P=0.040). Positive protein expression of TTF1 (P=0.010) and CK7 (P=0.001) was significantly more prevalent in p-SQCC. p-SQCC had significantly higher gene expression of SPA (P=0.003), whereas c-SQCC showed higher gene expression of TP63 (P=0.028). Lung p-SQCC had distinctive clinicopathologic characteristics and molecular features compared to c-SQCC, but showed some similarity with adenocarcinoma (ADC).