The tumor-stromal interaction between the intratumoral Wnt1 and the stromal VEGF-A is associated with angiogenesis in squamous cell carcinomas of the lung

Abstract

7192 Background: Recent studies have reported that the tumor-stromal interaction plays an important role in the tumor progression. The Wnt signaling pathway is also considered to be implicated in the tumor progression through its target proteins. Therefore, we studied on intratumoral expression of Wnt1 in relation to expression of VEGF-A, one of the Wnt-target proteins, among patients with non-small cell lung cancer (NSCLC). Methods: We studied 199 NSCLC patients who underwent at the Second Department of Surgery, Kagawa University from 1996 to 2003. By immunohistochemstry, we evaluated the intratumoral expression of Wnt1, the intratumoral expression of VEGF-A, and the stromal expression of VEGF-A, respectively. Furthermore, we evaluated the intratumoral microvessel density (IMD) using the anti-CD34 antibody. Results: (1) 73.3% of carcinomas had positive expression of Wnt1. There was no difference of intratumoral expression of Wnt1 in relation to tumor histology. The intratumoral expression of VEGF-A was significantly higher in adenocarcinomas than in squamous cell carcinomas (p=0.038). In contrast, the stromal expression of VEGF-A was significantly higher in squamous cell carcinomas than in adenocarcinomas (p<0.001). (2) Among squamous cell carcinomas, the intratumoral VEGF-A expression was likely to be higher in Wnt1-positive tumors than in Wnt1-negative tumors (p=0.053). Furthermore, the stromal VEGF-A expression was significantly higher in Wnt1-positive squamous cell carcinomas than in Wnt1-negative squamous cell carcinomas (p<0.001). In addition, the IMD was significantly higher in squamous cell carcinomas with positive expression of stromal VEGF-A than in those with negative expression of stromal VEGF-A (p=0.008). However, there was no significant correlation between the intratumoral Wnt1 expression and VEGF-A expression in adenocarcinomas. Conclusions: The stromal VEGF-A expression induced by intratumoral Wnt1 was associated with tumor angiogenesis in squamous cell carcinomas of the lung. The Wnt signaling pathway plays an role in the tumor-stromal interaction. No significant financial relationships to disclose.