Abstract 2685: The intratumoral expression of survivin associated with Wnt1 expression, not Wnt5a expression in non-small cell lung cancer

Abstract

Abstract Introduction: Survivin is a member of the inhibitor of apoptosis protein (IAP) family. Recent studies have revealed that survivin is associated not only with apoptosis but also with cell proliferation. As a result, the survivin expression is considered to be involved in tumorigenesis, including non-small cell lung cancer (NSCLC). On the other hand, the Wnt genes are involved in embryogenesis and tumorigenesis. Among them, Wnt1 stimulates the canonical Wnt signaling pathway, which regulates the transcription of various tumor-associated Wnt-target genes with TCF/LEF1 motif. We have reported that Wnt1 overexpression promotes tumorigenesis in NSCLC through the induction of c-Myc, cyclin D1, VEGF-A (Huang C, et al. Eur J Cancer 2008). Recently, survivin is also reported to be a target gene of the canonical Wnt signaling pathway. Therefore, we performed a clinical study on survivin expression in relation to the expression of Wnt1 (canonical Wnt) and Wnt5a (non-canonical Wnt) in NSCLC. Method: One hundred and ten NSCLC patients were investigated. The expression of wild-type survivin (survivin) was evaluated by semi-quantitative RT-PCR because real-time RT-PCR is not an appropriate method to discriminate between wild-type survivin and other splice variants, such as survivin-2B and survivin-deltaEx3. The intratumoral expressions of survivin, Wnt1 and Wnt5a were evaluated by immunohistochemistry. The Ki-67 proliferation index was also investigated by immunohistochemistry, and the apoptotic index was evaluated by TUNEL method. Results: (1) Sixty carcinomas (54.5%) had an overexpression of survivin. The apoptotic index was significantly lower in survivin-high tumors than in survivin-low tumors (P=0.003). In addition, the Ki-67 proliferation index was significantly higher in survivin-high tumors than in survivin-low tumors (P=0.014). (2) The percentage of Wnt1-positive tumor cells significantly correlated with the survivin gene expression (P<0.001). The survivin gene expression was significantly higher in Wnt1-positive tumors than in Wnt1-negative tumors (P=0.002). (3) The percentage of Wnt5a-positive tumor cells did not correlate with the survivin gene expression (P=0.155). There was no difference in the survivin gene expression according to the Wnt5a expression. (4) As a result, the apoptotic index was significantly lower in Wnt1-high tumors than in Wnt1-low tumors (P=0.032). In addition, the Ki-67 proliferation index was significantly higher in Wnt1-high tumors than in Wnt1-low tumors (P=0.001). Conclusions: The intratumoral Wnt1 expression affects the expression of wild-type survivin in NSCLC to produce more aggressive tumors with low tumor apoptosis and high tumor proliferation rate. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2685.