Neurotrophic Tyrosine Kinase Receptor Type 1 and 2 (NTRKA and NTRKB) Expression in Non Small Cell Lung Cancers (NSCLC)
Katsiaryna Laziuk, Ashley Tarasen, Christine E Sheehan, Jeffrey S Ross. Albany Medical College, Albany, NY
Background: The NTRKA and NTRKB genes encode for tyrosine kinase receptors that regulate the MAPK pathway and play roles in neuronal development and differentiation. NTRKA and NTRKB mutations have been reported in NSCLC, but their prognostic significance is not currently known.
Design: Formalin-fixed, paraffin-embedded sections from 138 NSCLC, including 42 squamous cell carcinomas (SCC), 63 adenocarcinomas (AC), and 33 bronchoalveolar carcinomas (BAC), were immunostained by a manual method with NTRKA and NTRKB rabbit monoclonal antibodies (Cell Signaling Technology, Danvers, MA). The staining pattern was semiquantitatively assessed based on staining intensity and distribution and the results were correlated with morphologic and prognostic variables.
Results: Immunoreactivity for NTRKA and NTRKB was predominately cytoplasmic. NTRKA overexpression was noted in 36/138 (26%) tumors and correlated with tumor type [50% SCC vs 21% AC vs 6% BAC, p<0.0001] and high grade [32% high vs 4% low, p=0.003], and male gender (34% male vs 16% female, p=0.016). NTRKB overexpression was noted in 27/138 (20%) tumors and correlated with tumor type [52% SCC vs 8% AC vs 0% BAC, p<0.0001] and high grade [27% high vs 0% low, p=0.002], and male gender (29% male vs 7% female, p=0.001), while showing a trend toward correlation with tumor size [28% >= 3.0 cm vs 15% < 3.0cm, p=0.076). There was significant co-expression of the two proteins (p<0.0001). On multivariate analysis, advanced stage (p=0.002) independently predict shortened survival.
Conclusions: Increased expression of NTRKA and NTRKB protein in NSCLC is associated with tumor subtype and grade in NSCLC. Given the recent evidence that NSCLC harboring a gene fusion based activation of NTRKA could be sensitive to tyrosine kinase inhibitors, further study of NTRK expression in NSCLC appears warranted.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 290, Monday Morning