Expression and significance of PTEN, hypoxia-inducible factor-1 alpha in colorectal adenoma and adenocarcinoma

AIM: To investigate the expression and significance of PTEN, hypoxia-inducible factor-1 alpha (HIF-lalpha), and targeting gene VEGF during colorectal carciogenesis. METHODS: Total 71 cases colorectal neoplasms (9 cases of colorectal adenoma and 62 colorectal adenocarcinoma) were formalin fixed and paraffin-embedded, and all specimens were evaluated for PTEN mRNA, HIF-1alpha mRNA and VEGF protein expression. PTEN mRNA, HIF-1alpha mRNA were detected by in situ hybridization. VEGF protein was identified by citrate-microwave SP immunohistochemical method. RESULTS: There were significant differences in PTEN, HIF-1alpha and VEGF expression between colorectal adenomas and colorectal adenocarcinoma (P<0.05). The level of PTEN expression decreased as the pathologic stage increased. Conversely, HIF-1alpha and VEGF expression increased with the Dukes stage as follows: stage A (0.1029 +/- 0.0457: 0.1207 +/- 0.0436), stage B (0.1656 +/- 0.0329: 0.1572 +/- 0.0514), and stage C+D (0.2335 +/- 0.0748: 0.2219 +/- 0.0803). For PTEN expression, there was a significant difference among Dukes stage A, B, and C+D, and the level of PTEN expression was found to be significant higher in Dukes stage A or B than that of Dukes stage C or D. For HIF-1alpha expression, there was a significant difference between Dukes stage A and B, and the level of HIF-1alpha expression was found to be significantly higher in Dukes stage C+D than that of Dukes stage A or B. The VEGF expression had similar results as HIF-1alpha expression. In colorectal adenocarcinoma, decreased levels of PTEN were significantly associated with increased expression of HIF-1alpha mRNA (r=-0.36, P<0.05) and VEGF protein (r=-0.48, P<0.05) respectively. The levels of HIF-1 were positively correlated with VEGF expression (r=0.71, P<0.01). CONCLUSION: Loss of PTEN expression and increased levels of HIF-1alpha and VEGF may play an important role in carcinogenesis and progression of colorectal adenocarcinoma.