NTRK2 Expression Predicts Improved Disease Specific Survival in Squamous Cell Carcinoma of Lung
J Terry, A DeLuca, S Leung, G Peacock, YZ Wang, WM Elliot, D Huntsman. BC Cancer Agency, Vancouver, BC, Canada; UBC-James Hogg iCAPTURE Centre, Vancouver, BC, Canada
Background: The neurotrophic tyrosine kinase receptors NTRK1 (TRKA) and NTRK2 (TRKB) are oncoproteins belonging to a family of nerve growth factor receptors that normally regulate nervous system development. NTRK1 and 2 abnormalities have been reported in neoplasms of lung, suggesting a pathogenic role; however, the significance of NTRK1 and 2 expression in lung cancer is unclear.
Design: Normal control tissues and 713 individual lung cancer cases with long-term clinical outcome data in tissue microarray format are immunohistochemically stained for NTRK1 and NTRK2 using commercially available antibodies, automated staining and standard protocols. Positive staining is defined as any amount of membranous staining within tumor tissue in at least one tumor core. Statistical analyses are performed on SPSS v16.0.
Results: Both NTRK1 and NTRK2 show strong correlation to squamous carcinoma of lung (NTRK1: 211/282 positive, 95% specific and 75% sensitive, Kendall tau-b = 0.730 p << 0.05; NTRK2: 139/282 positive, 96% specific and 49% sensitive, Kendall tau-b = 0.529 p << 0.05). Positive staining is less frequent in adenocarcinoma (NTRK1: 12/248, NTRK2: 11/248), bronchioloalveolar carcinoma (1: 0/8, 2: 0/8), carcinoid tumor (1: 2/93, 2: 1/93), large cell carcinoma (1: 5/60, 2: 4/60), large cell neuroendocrine tumor (1: 0/6, 2: 2/6), and small cell carcinoma (1: 0/13, 2: 0/13). There is significant correlation between positive NTRK2 staining and improved disease specific survival in squamous carcinoma (Log rank test: chi2 = 14.4, p = 1.46x10-4) while NTRK1 staining has no prognostic significance. Positive NTRK2 staining is not frequent enough in other lung cancer subtypes to achieve statistically reliable correlations with patient outcome. NTRK1 staining is present in normal squamous epithelium from skin and tongue (3/3) but not normal lung (0/1) whereas NTRK2 staining is present in brain (1/1) but not in lung (0/1) or squamous epithelium (0/3) and appears to be cancer specific.
Conclusions: Positive NTRK2 staining predicts significantly improved disease specific survival in patients with squamous carcinoma of lung. Both NTRK1 and 2 are highly specific markers of squamous lung carcinoma; however, NTRK2 expression appears restricted to neoplastic squamous lung epithelium and may identify a subset of lung cancer with unique pathogenesis amenable to therapies targeting the NTRK2 signaling pathway.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 242, Tuesday Afternoon