Immunohistochemical Expression of Neurotrophic Tyrosine Kinase Receptors 1 and 2 in Lung Carcinoma: Potential Discriminators Between Squamous and Nonsquamous Subtypes

Abstract

The neurotrophic tyrosine kinase receptors NTRK1 and NTRK2 have been implicated in the pathogenesis of lung carcinomas. NTRK receptor expression has been reported in lung carcinomas; however, the clinical utility of immunohistochemical expression of these receptors is unclear. To compare the immunohistochemical expression profiles of NTRK1 and NTRK2 in various histologic subtypes of lung carcinomas and correlate with patient outcome. Six hundred eighty-six unique lung cancer cases (including squamous cell carcinoma, adenocarcinoma, large cell carcinoma, small cell carcinoma, and carcinoid tumor) with clinical outcome data in tissue microarray format were immunohistochemically stained for NTRK1 and NTRK2 using commercially available antibodies, automated immunostaining, and standard protocols. Expression of both NTRK1 and NTRK2 correlates strongly with squamous histology. NTRK1 and NTRK2 are highly specific markers (1: 92.8%, 2: 96.4%) of squamous lung carcinoma when compared with the other carcinoma subtypes, including adenocarcinoma. Positive NTRK2 staining in squamous carcinoma correlates with improved disease-specific survival (P < .001) and overall survival (P = .047). NTRK1 and NTRK2 are potentially useful immunohistochemical markers that may be particularly helpful in separating squamous cell carcinoma from adenocarcinoma.