Vascular endothelial growth factor-C expression and lymphangiogenesis in colorectal cancer

Abstract

BACKGROUND: Colorectal cancer is a common cause of death throughout the world. Approximately 145,290 new cases of large bowel cancer are diagnosed each year in the United States, of which 104,950 are colon and the remainder rectal cancers. In 2005, more than 56,000 Americans will die of CRC, accounting for approximately 10 percent of all cancer deaths. In the United States, CRC ranks second to lung cancer as a cause of cancer death, and it is third both in frequency and cause of cancer death, in men and women separately. In 2004 in Europe, there were an estimated 2 886 800 incident cases of cancer diagnosed and 1 711 000 cancer deaths. The most common incident form of cancer was lung cancer (13.3 % of all incident cases), followed by colorectal cancer (13.2 %) and breast cancer (13 %). Lung cancer was also the most common cause of cancer death (341 800 deaths), followed by colorectal (203 700), stomach (137 900) and breast (129 900). According to the ASO-ASSO (Austrian Society of Surgical Oncology) in Austria CRC is the second most common cancer and the incidence rate is increasing. As in many types of cancer, the lymphatic system is the primary pathway of metastasis, representing the first step of generalisation. However, lymphangiogenesis and the mechanism of lymphatic metastasis in colorectal cancer remain unclear. Aim of this study was to investigate the prognostic role of lymphangiogenesis (LMVD), lymphovascular invasion (LVI) and the lymphangiogenic growth factor VEGF-C in a cohort of colorectal cancers. METHODS: Forty-seven cases of colorectal cancer were investigated. VEGF-C-expression, LMVD, LVI and lymphatic vessel size (LVS) were evaluated semiquantitatively by immunohistochemistry. RESULTS: A significant association was seen between LMVD and LVI (p ≤ 0.005, Mann-Whitney test). LVI correlated significantly with the lymph-node status (p = 0.04, Spearman's coefficient of correlation) and LVS (p = 0.018, Mann-Whitney test). In a mean observation time of 145 months univariate survival analysis showed a significant difference in disease-free survival (DFS) and a clear trend in overall survival (OS) between patients with and without LVI (p = 0.0148 and p = 0.14, respectively, log-rank test). Further VEGF-C-expression in tumor-cells had a significant influence on the OS in univariate survival analysis (p = 0.0391, log-rank test). CONCLUSIONS: These data provide further evidence for the important role of lymphangiogenesis and lymphovascular invasion in the prognosis of colorectal cancer implying new potential anti-tumor targets.