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

Abstract

Context.—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. Objective.—To compare the immunohistochemical expression profiles of NTRK1 and NTRK2 in various histologic subtypes of lung carcinomas and correlate with patient outcome. Design.—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. Results.—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). Conclusions.—NTRK1 and NTRK2 are potentially useful immunohistochemical markers that may be particularly helpful in separating squamous cell carcinoma from adenocarcinoma.

New immunohistochemical markers in the differential diagnosisof nonsmall cell lung carcinoma

“…In another study investigating 686 primary pulmonary cancers, NTRK-1 showed high specificity (92.8%) but relatively low sensitivity (71.6%) in SqCC (10). In the same study, NTRK-2 was also found to be specific (96.4%) for SqCC but with quite low sensitivity (51.3%).…”

“…A study suggested that NTRK-1 staining does not have a significant effect on the prognosis of SqCC and AC but is a positive prognostic factor for SqCC in patient survival irrespective of sex, stage, age, and smoking (10). They observed improvements in the disease-related survivals of NTRK-2 positive SqCC cases but the effect of NTRK-2 on survival in AC cases was statistically insignificant (10).…”

“…A study suggested that NTRK-1 staining does not have a significant effect on the prognosis of SqCC and AC but is a positive prognostic factor for SqCC in patient survival irrespective of sex, stage, age, and smoking (10). They observed improvements in the disease-related survivals of NTRK-2 positive SqCC cases but the effect of NTRK-2 on survival in AC cases was statistically insignificant (10). Contrasting this, we found that disease-free survival time was significantly shorter in moderately NTRK-1 positive stained cases compared with mildly positive cases, irrespective of the histological subtype and independent of other variables.…”

“…NTRK-1 and NTRK-2 have been found to be expressed more strongely in immunohistochemical terms in squamous differentiation than in glandular differentiation. It has been reported that they can be useful in distinguishing SqCC from AC, especially in small samples such as needle biopsies that cannot be diagnosed in histological terms (6,10).…”

Identification of prognostically relevant gene signatures in lung squamous cell carcinoma by Lung Cancer Explorer

“…In particular, SOX2 and TP63, which are stem markers and lineage drivers in squamous carcinoma, were demonstrated to be oncogenic drivers and were commonly used to identify the pathological subtype between adenocarcinoma and squamous cell carcinoma (17,18). Similarly, NTRK2 was found to be a highly specific marker of squamous lung carcinoma compared to other pathological subtypes, including adenocarcinoma (19). These genes were found to be in favour of the overall survival of lung squamous cell carcinoma patients, which was demonstrated in earlier articles (19)(20)(21) and confirmed in our study.…”