HER3 expression and MEK activation in non-small-cell lung carcinoma
Thubeena Manickavasagar, Wei Yuan, Suzanne Carreira, Bora Gürel, Susana Miranda, Ana Ferreira, Mateus Crespo, Ruth Riisnaes, Chloe Baker, Mary O’Brien, Jaishree Bhosle, Sanjay Popat, Udai Banerji, Juanita Lopez, Johann S. de Bono, Anna Minchom
Abstract
Aim: We explore HER3 expression in lung adenocarcinoma (adeno-NSCLC) and identify potential mechanisms of HER3 expression. Materials & methods: Tumor samples from 45 patients with adeno-NSCLC were analyzed. HER3 and HER2 expression were identified using immunohistochemistry and bioinformatic interrogation of The Cancer Genome Atlas (TCGA). Results: HER3 was highly expressed in 42.2% of cases. ERBB3 copy number did not account for HER3 overexpression. Bioinformatic analysis of TCGA demonstrated that MEK activity score (a surrogate of functional signaling) did not correlate with HER3 ligands. ERBB3 RNA expression levels were significantly correlated with MEK activity after adjusting for EGFR expression. Conclusion: HER3 expression is common and is a potential therapeutic target by virtue of frequent overexpression and functional downstream signaling.