Expression and significance of PTEN, hypoxia-inducible factor-1 alpha in colorectal adenoma and adenocarcinoma.
OBJECTIVE
To investigate the expression and significance of PTEN, hypoxia-inducible factor-1 alpha (HIF-1alpha), 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).


CONCLUSIONS
Loss of PTEN expression and increased levels of HIF-1alpha and VEGF may play an important role in carcinogenesis and progression of colorectal adenocarcinoma.
Jiang
Ying-An
YA
Department of Gastroenterology, Renming Hospital of Wuhan University, Wuhan 435000, Hubei Province, China. hszxyy@public.hs.hb.cn
Fan
Li-Fang
LF
Jiang
Chong-Qing
CQ
Zhang
You-Yuan
YY
Luo
He-Sheng
HS
Tang
Zhi-Jiao
ZJ
Xia
Dong
D
Wang
Ming
M
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins / Q000378:metabolism*; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human