Survivin and CrkL expression in erlotinib-treated non-small cell lung cancer (NSCLC) patients (p) with EGFR mutations.

Abstract

e18063 Background: Survivin inhibits activation of caspas es, and its overexpr ession can lead to resistance to apoptotic stimuli. Enhanced survivin expression has been shown to be related to IGF-1R activity. CrkL is a 39-kDa tyrosine-phosphorylated adaptor protein that is involved in leukemia cell signalling and is an important substrate of Bcr-Abl. Methods: Survivin and CrkL protein expression were ass essed by immunohistochemical (IHC) staining in original pretreatment tumor biopsies of 126 NSCLC p with EGFR mutations, in whom IGF-1R expr ession had previously been examined. IHC was evaluated semiquantitatively and scored according to the percentage of cells showing distinct nuclear and/or cytoplasmic reaction and the intensity of IHC. Tumors with a score of 0 or 1 were defined as negative and those with a score of 2 or 3 were defined as positive. IHC intensity was correlated with outcome to erlotinib. Results: There was no correlation between the expression of survivin and CrkL (p = 0.16). A correlation was observed between survivin and IGF-1R mRNA levels (r = 0.12; p = 0.005). No differences were observed in the expression of the two proteins according to gender, smoking history, PS, type of EGFR mutation, metastatic site, or other clinical characteristics. Overall response rate (RR) was 70%, progr ession-free survival (PFS) was 14 months (m), and median survival (MS) was 27 m. No differenc es in RR were observed according to the expression of either of the proteins. PFS for the 17 p with negative survivin was 24 m vs 14 m for 109 p with positive survivin (p = 0.11). MS was 36 m for p with negative survivin and 27 m for those with positive survivin (p = 0.004). No differences in PFS or MS were observed according to CrkL expr ession. Conclusions: Negative survivin protein expression is observed in a small number of patients with EGFR mutations and confers improved survival. No significant financial relationships to disclose.