Published online Mar 15, 2003. doi: 10.3748/wjg.v9.i3.491
Revised: December 23, 2002
Accepted: January 9, 2003
Published online: March 15, 2003
AIM: To investigate the expression and significance of PTEN, hypoxia-inducible factor-1 alpha (HIF-1α), 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-1α mRNA and VEGF protein expression. PTEN mRNA, HIF-1α 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-1α 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-1α 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-1α expression, there was a significant difference between Dukes stage A and B, and the level of HIF-1α 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-1α expression. In colorectal adenocarcinoma, decreased levels of PTEN were significantly associated with increased expression of HIF-1α 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-1α and VEGF may play an important role in carcinogenesis and progression of colorectal adenocarcinoma.