Prognostic Significance of Immunohistochemical Surrogate Molecular Sub-Typing of Small Cell Lung Carcinoma

Abstract

Small cell lung carcinoma (SCLC) was considered a homogenous tumor both morphologically and genetically. Gene expression profiling of SCLC has revealed existence of four distinct subtypes within the SCLC which may impact the prognosis and therapeutic outcome. In the present study, surrogate molecular subtyping of SCLC was done using immunohistochemistry. Histologically confirmed cases of SCLC were included in the study. For molecular sub-typing, primary antibodies specific for ASCL1, POU2F3, NEUROD1, and YAP1 were used. The results were also correlated with baseline demographic and clinical parameters as well as treatment outcome. ASCL1, NEUROD1, and POU2F3 were expressed in 68 (67.3%), 15 (14.9%) and 3 (3.0%) cases, respectively. YAP1 showed cytoplasmic expression in 3 cases (3.0%). ASCL1 and NEUROD1 were co-expressed in 6.9% of cases. The remaining 25.7% of cases were negative for or had low expression of all four transcription factors. SCLC cases were thus classified as ASCL1-dominant, NEUROD1-dominant, ASCL1/NEUROD1 co-expressing, POU2F3-dominant, and Quadruple-negative subtypes. We did not recognize the YAP1 subtype. The overall survival was significantly reduced in the ASCL1 subtype compared to other subtypes. Sub-classification of SCLC patients may help in predicting the prognosis in such patients and may also help in guiding the therapy in the future.

Keywords: ASCL1; NEUROD1; POU2F3; lung cancer; small cell.