Expression of LDH-5 in Colorectal Carcinomas: Correlation with Prognosis and Tumor Angiogenesis

ABSTRACT

PURPOSE: Lactate dehydrogenase-5 (LDH-5) is one of five isoenzymes and is the most important for anaerobic glycolysis. LDH-5 is transcriptionally regulated by hypoxia-inducible factor (HIF). HIF plays a role in the response to hypoxia by activating genes involved in vascular remodeling, cell proliferation, and erythropoiesis. In this study, we investigated the clinicopathologic significance and angiogenesis of LDH-5 expression in colorectal cancer. METHODS: We retrospectively reviewed the medical records of 83 patients with colorectal cancer who underwent a surgical resection at Soonchunhyang Cheonan Hospital from January 2001 to December 2003. LDH-5 and HIF-1alpha protein expressions were evaluated in 83 human colorectal cancer specimens. These factors were related to TNM stage, lymph node metastasis, vascular, neural, and lymphatic invasion, and prognosis. RESULTS: LDH-5 was positive in 66% (55 patients) of the tumors, and HIF-1alpha was positive in 66% (55 patients) of the tumors. LDH-5 expression was significantly associated with HIF-1alpha protein expression (P<0.001). Also, LDH-5 expression was significantly associated with TNM stage and lymph node metastasis (P<0.001) while HIF-1alpha expression was significantly associated with TNM stage (P<0.001), lymph node metastasis (P<0.001), vascular invasion (P=0.011), and lymphatic invasion (P=0.005). The survival of the patients with high LDH-5 expression was worse than that of patients with low LDH-5 expression (P=0.032). CONCLUSION: Our study shows a high expression of LDH-5 in colorectal cancer. The up-regulation of LDH-5 parallels an increase in HIF-1alpha expression. The immunohistochemical assessment of tissue LDH-5 and HIF-1alpha provides important prognostic information for colorectal carcinomas.