| Hypoxia is a basic characteristic of micro-enviroment of solid tumors. Angiogenesis and celluar adaptation to hypoxia represent a critical step in tumorigenesis. The key factor regulating cellular 62 homeostasis is hypoxia-inducible factor-1 (HIF-1), which transcriptionally regulate expression of several dozens of the target genes. HIF-1 activates transcription of the genes that are involved in crucial aspects of cancer biology,including angiogenesis, cell survival,glucose metabolism ,invasion and metastasis. HIF-1 is a heterodimeric complex composed of HIF-1 a and HIF-1β, the former is the unique, O-regulatid subunit that determines HIF-1 activity. Untill now vascular endothelial growth factor(VEGF) is the most prominent angiogenic growth factor, whose expression is regulated by some factors,of which hypoxia is the strongest inducer of VEGF expression. CD34 is widely used in marking vascular endothelial cell and detecting microvessel density(MVD).The specificity of CD34 antigen is higher than others. In order to evaluate the role of HIF-1 a protein in tumorigenesis of colorectal adenocarcinoma and its relationship with VEGF and MVD, inmunohistochemical technique was applied to examining expression of HIF-1 a ,VEGF and CD34, which may provide theoretical foundation for antiangiogenic therapies of colorectal cancers.Material and Methods: The expressions of HIF-1 a protein ,VEGF and CD34 in 50 cases of colorectal adenocarcinoma tissues, 17 cases of colorectal adenomas and 12 cases of normal colorectal tissues were examined by using S-P immunohistochemistry.-4-SPSS 10.0 was used to evaluate the statistical significance.Results: (1) In normal colorectal tissues, colorectal adenomas and colorectal adenocarcinoma, the positive rates of HIF-1 a were (8.3%, 1/12), (47.1%, 8/17), and (64%, 32/50), respectively. There were significant differences (PO.05 ) when colorectal adenomas and colorectal adenocarcinoma compared with normal colorectal tissues.(2) The positive rates of VEGF in colorectal adenocarcinoma (62%, 31/50)were significantly higher than that of normal colorectal tissues (0%, 0/12) and colorectal adenomas (29.4%, 5/17) (P<0.05) .There were significant differences (P0.05) when the groups compared with each other.(3) MVD in colorectal adenocarcinoma tissues (22.31 ?6.05) and colorectal adenomas(12.48 ?3.87) was significantly higher than that of normal colorectal tissues(7.80?.34) (P<0.01) . There were significant differences (P0.05) when the groups compared with each other; MVD in pathologic stage of the specimens were as follows-.Dukes A ( 16.02 + 4.29 X Dukes 8(18.45 ?.08) Dukes C+D(26.31?.20). There were significant differences (P0.05) when Dukes C+D compared with Dukes A and Dukes B, respectively .(4) The positive rates of HIF-1 a were correlated to the depth of invasion, lymph node metastasis. HIF-1 a with lymph node metastasis (85.7%, 18/21 ) was significantly higher than that without lymph node metastasis48.2% (14/29) (P0.01) . HIF-1 a without penetrating serosa (41.2%, 7/17) was significantly lower than that with penetrating serosa ( 75.8%, 25/33 ) (P0.05 ) . The mean percentage of HIF-1 a positive cells increased gradually with the development from Dukes stage A to stage C+D(P0.05) . The frequencies of HIF-1 a positive cells in pathologic stage of the specimens were as follows:Dukes A ( 37.5%, 3/8 ) Dukes B ( 46.7%, 7/15), Dukes C+D(81.5%, 22/27) . There were significant differences (P0.05) when Dukes C+D compared with Dukes A. HIF-1 a was not correlated with the extent of differentiation(P>0.05) .(5) The positive rates of VEGF were correlated to the depth of invasion, lymph node and distant metastasis.The positive rates of VEGF with lymph node metastasis (81%,-5-17/21) was significantly higher than that without lymph node metastasis ( 48.3%, 1 4/29 ) (PO.05). VEGF without penetrating serosa (41.2%, 7/17) was significantly lower than that with penetrating serosa (72.8%, 24/33) (P<0.05); No correlation of VEGF expression with the extent of di...
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