P3.01-032 PELP1 Expression in Molecularly Classified Lung Adenocarcinomas: Topic: Morphology

Abstract

Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a scaffolding protein which functions as a coregulator of several transcription factors and nuclear receptors. It has a histone-binding domain and plays essential roles in several pathways including hormonal signaling. PELP1 is a coregulator of estrogen receptor (ER) and has been shown to be deregulated, contributing to therapy resistance and is a prognostic biomarker in breast cancer survival, as well as in other hormone-dependent cancers. Estrogens are also known to enhance lung tumorigenesis by estrogen receptor pathway.1,2 In this study, we investigated the expression of PELP1 in molecularly classified lung adenocarcinomas, specifically those with known EGFR and KRAS mutations. Tissue microarray (TMA) was created using 0.6 mm tissue cores in triplicates from 62 resected lung adenocarcinoma cases (26 with EGFR mutation and 36 with KRAS mutation). PELP1 antibody (Clone EPR15212; ABCAM) immunostaining was performed after heat induced epitope retrieval. Nuclear immunoreactivity for PELP1 was scored for staining intensity as 0 (negative), 1+ (weak, nucleolar), 2+ (moderate, nucleolar/nuclear) and 3+ (strong nucleolar/nuclear). For statistical analysis, binary split was done as negative (scores 0 and 1+) and positive (scores 2+ and 3+). These TMAs were also stained for estrogen receptor (ER) with SP1 rabbit monoclonal antibody and scored similarly. In our study, 61 cases had evaluable tissue cores with tumor. Positive PELP1 expression was noted in 14/25 (56%) EGFR mutated and 30/36 (83%) in KRAS mutated lung adenocarcinomas (p<0.05). From the EGFR-mutated group, 4/25 (16%) reveal weak (1+) and focal staining for ER while one case revealed strong ER staining. From the KRAS-mutated group, 2/36 (5%) cases revealed weak (1+) staining for ER. All these cases with ER positivity (7/61; 11.5%) (weak/strong) were also positive for PELP1. Our study has demonstrated that apart from PELP1 expression in ER positive lung adenocarcinomas, it can also be seen in estrogen receptor negative molecularly classified lung adenocarcinomas. It is more often seen in KRAS mutated lung adenocarcinomas. Estrogen receptor independent PELP1 expression in lung adenocarcinoma suggests presence of alternate pathways for tumorigenesis or tumor progression, which needs further investigation; especially in KRAS mutated lung adenocarcinomas.