P1.02-075 Analysis of Driver Genes Alteration and Clinicopathological Features in Pulmonary Marker-Null Large Cell Carcinoma

Abstract

Pulmonary large cell carcinoma (LCC) was an undifferentiated and marker-null non-small cell lung cancer (NSCLC) according to 2015 WHO classification criteria. However, there are few studies presented molecular analysis and clinical features of this subtype. The aim of this study is to investigate profile of driver mutations and clinicopathological features of marker-null LCC. From January 2008 to February 2015, 327 cases of surgically resected primary large cell carcinoma diagnosed by H&E staining were enrolled from Shanghai pulmonary hospital affiliated to Tongji university (Lymphoepithelioma-like carcinoma and large cell neuroendocrine carcinoma were excluded with typical morphologic features). Large cell carcinoma was re-classificated with a panel of immunophenotypic markers (adenocarcinoma [ADC]-specific, thyroid transcription factor-1, napsin A and anti-diastase PAS staining; squamous cell carcinoma [SQCC]-specific, cytokeratin5/6, and p40; epithelial mesenchymal transition [EMT], cytokeratin, vimentin and ZEB1; neuroendocrine differentiation, synaptophysin and CD56). Molecular analysis (EGFR, KRAS, BRAF, ROS1, ALK and PIK3CA) and immunomarker PD-L1 of marker-null LCC were detected by ARMS method and immunohistochemistry, respectively. 113 cases (113/327, 34.6%) were re-diagnosed as ADC with solid growth pattern, which showed TTF-1 positive rate 59.3% (67/113, 59.3%), Napsin A positive rate 82.3% (93/113，82.3%) (P<0.001) and positive PAS staining (5/113, 4.4%). 47 (47/327, 14.4%) cases were re-classificated as SQCC, which positively expressed p40 (44 cases, 44/47, 93.6%) and CK5/6 (31 cases, 31/47, 66%)( P<0.01). 5 (5/327, 1.5%) cases of large cell neuroendcrine carcinoma showed both neuroendocrine morphological feature and CD56、Syn expression. 26 (26/327, 8.0%) were redefined as sarcomatoid carcinoma expressed cytokeratin, vimentin and ZEB1. 136 (136/327, 41.6%) cases of marker-null LCC were diagnosed for lack of specific markers expression. 30 (30/136, 22.1%) cases of marker-null LCC showed PD-L1 positive. Driver genes alteration were found in 3 cases from 30 cases marker-null LCC, including KRAS (n=1), BRAF (n=1) and PIK3CA (n=1). Clinicopathological characteristics indicated that LCC patients were older and more likely to be male nonsmokers. Large cell carcinoma was differentially diagnosed by combining with undifferentiated NSCLC morphology and marker-null features. Driver genes mutation testing may significantly impact on the choice of targeted therapy.