Insulin-like growth factor receptor 1 (IGF1R) protein expression, mRNA expression and gene copy number in operable non-small cell lung cancer (NSCLC)

Abstract

7524 Background: IGF1R is a promising target for NSCLC therapy. We have evaluated IGF1R protein expression, mRNA expression and gene copy number in primary tumors from surgically treated NSCLC patients (pts) as a reference for correlative biomarker studies in trials using IGF1R inhibitors. Methods: The study included 189 consecutive NSCLC pts who underwent curative pulmonary resection. There were 24% females, 54% squamous cell carcinomas (SCC), 29% adenocarcinomas (AC), 3% large cell carcinomas, 14% other histologies; p stage I: 41%, pII: 22%, pIII: 32% and pIV: 4%. IGF1R expression was evaluated in tissue microarrays by immunohistochemistry (IHC) with Ventana CONFIRM (N=179) and Novus (#NB600–559) anti-IGF1R Ab scored by two observers (H score 0–400). IGF1R gene copy number was assessed by FISH using customized probes (N=181). IGF1R gene expression was evaluated using qRT-PCR from 114 corresponding fresh-frozen samples. Results: Patterns of IHC staining were different for the Ventana and the Novus Ab (inverse correlation, r=-0.16, p=0.04, N=177). IGF1R protein expression detected by Ventana Ab (> median score) was more frequent in SCC (76%) than AC and other histologies (14%, p<0.001) and in pts with higher stage (p=0.03) but was not associated with survival (p=0.46). IGF1R H score by Ventana Ab, but not by Novus Ab, correlated with mRNA expression (r=0.37, p<0.001). IGF1R mRNA expression tended to be higher in SCC than in other histologies (p=0.089), but did not associate with other clinical features or survival (p=0.73). According to criteria previously established for EGFR, IGF1R gene copy number by FISH showed 5 tumors with gene amplification (2.8%), 43 tumors - high polysomy (23.8%), 87 tumors - low polysomy (48.1%), and 46 tumors - trisomy/disomy (25.4%). Pts with gene amplification/high polysomy had 3-yr survival of 60% (95% CI 47% - 74%) vs. 48% (38% - 59%) for low polysomy and 35% (21% - 49%) for trisomy/disomy pts (p=0.016). Prognostic value of IGF1R gene copy number was confirmed in the multivariate analysis. Conclusions: IGF1R protein expression is higher in SCC. IGF1R protein and gene expression does not associate with survival, whereas high IGF1R gene copy number associates with better prognosis in operable NSCLC. [Table: see text]