Abstract 345: The intratumoral Wnt2B expression affects tumor progression in malignant pleural mesotheliomas

Abstract

Abstract Introduction: Malignant pleural mesotheliomas are aggressive tumors with a poor prognosis. It is considered to be important to identify the molecular targets for the treatment against malignant pleural mesotheliomas. We have recently found the Wnt1 expression to affect tumor progression in non-small cell lung cancers, through the induction of various Wnt-targets (Huang et al, Eur J Cancer 2008). Therefore, we performed a clinical study on the intratumoral expressions of the canonical Wnts, such as Wnt1 and Wnt2B, in relation to their targets, including c-Myc and survivin. Methods: Sixty-five cases with malignant pleural mesotheliomas were investigated. Immunohistochemical assays were performed to evaluate the intratumoral expressions of Wnt1, Wnt2B, c-Myc and survivin. In addition, the Ki-67 proliferation index was evaluated by immunohistochemistry, and the apoptotic index was evaluated by the TUNEL method. Results: The Ki-67 proliferation index was significantly higher in c-Myc-high tumors than in c-Myc-low tumors (P=0.008). In addition, the Ki-67 proliferation index was also significantly higher nuclear-survivin-high tumors than in nuclear-survivin-low tumors (P=0.004). Regarding the intratumoral expressions of canonical Wnts, 18 tumors (27.7%) were Wnt1-high tumors, and 36 tumors (55.4%) were Wnt2B-high tumors. The rate of Wnt2B-high tumors was significantly higher than the rate of Wnt1-high tumors (P=0.024). Regarding tumor histology, the Wnt2B expression was the significantly highest in epithelial type (P<0.001). On the other hand, there was no significant difference in the Wnt1 expression according to the tumor histology (P=0.163). Furthermore, the Wnt 2B expression significantly correlated with expressions of c-Myc and survivin (P<0.001 and P<0.001, respectively). The c-Myc expression was significantly higher in Wnt2B-high tumors than in Wnt2B-low tumors (P<0.001), and the survivin expression was also significantly higher in Wnt2B-high tumors than in Wnt2B-low tumors (P=0.007). In contrast, there was no significant difference in c-Myc or survivin expressions according to the Wnt1 expression (P=0.218 and P=0.688, respectively). Conclusions: The intratumoral Wnt2B expression affects tumor progression of malignant pleural mesothelioma through the induction of c-Myc and survivin. The Wnt2B could be a candidate of targets of the molecular therapy against malignant pleural mesotheliomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 345. doi:10.1158/1538-7445.AM2011-345