Avaliação da mutação de EGFR e da imunoexpressão de ALK e de PD-L1 em Adenocarcinomas de Pulmão

Abstract

Lung cancer is one the most frequent cause of cancer death in Brazil and worldwide. The advent of new drugs directed towards specific molecular alterations, such as anti-tyrosine kinase for EGFR mutation (Epidermal Growth Factor Receptor) and for the rearrangement of the ALK (Anaplastic Lymphoma Kinase) gene and immunotherapy for PD-L1 (Cell Death Ligant 1 Receptor)expression brought an important gain in overall survival and in progression free survival in patients with non-small cell lung cancer (NSCLC) harboring those alterations. The present study aims to investigate the biomarkers EGFR, ALK and PD-L1 and their relationship with demographic data and histologic growth patterns in pulmonary adenocarcinomas. The study consisted in a retrospective analysis involving 173 paraffin-embedded specimens of NSCLC from the registry of the pathology laboratory during 2015 and 2016. ALK and PD-L1 expression in tumor cells were evaluated by immunohistochemical analysis using antibodies D5F3 and SP263, respectively. EGFR mutation status was assessed through sequencing. ALK expression was detected in 10.4% of samples and the population with ALK positivity was, in average, 8.8 years younger than the population not expressing ALK (p=0.0034). 22% of tumors carried mutations in EGFR. The most frequent EGFR mutation was exon 21 L858R point mutation (45.5%) followed by exon 19 deletions (36.3%). Solid predominant subtype was associated with wild-type EGFR status (P=0.047). PD-L1 tumor proportion scores (TPS) of ≥50% was documented in 18.2% of samples. No significant relationships were found between positive PD-L1 expression and driver genes (neither ALK nor EGFR).