Expression Of Survivin And Its Relationship With Apoptosis, Proliferation, And Angiogenesis During Human Colorectal Tumorigenesis

Objective: To identify the role of surviving novel member of inhibitor of apoptosis proteins (lAPs) in colorectal tumorigenesis and examined whether the expression of survivin correlated with tumor cell apoptosis,proliferation,and angiogenesis.Methods: Expressions of survivin mRNA and Vascular endothelial growth factor (VEGF) mRNA were evaluated by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in 52 colorectal tumor samples and 48 adjacent normal colorectal tissue samples. The PCR products were sequenced to verify the disired results. Immunohistochemical assay was to detect the expression of survivin, VEGF proteins and proliferating cell nuclear antigen labelling index (PCNA LI), apoptotic index (AI),microvessel density (MVD) in human colorectal tumors including 15 polyps, 12 tubular adenomas, 16 villous adenoma or tubulovillous adenomas,and 52 carcinomas.Results: (1)Expressions of survivin mRNA and VEGF mRNA were detected in a significantly greater proportion of colorectal carcinoma samples (67.3%,76.9%) than adjacent normal colorectal tissues (25%,52.1%). (P<0.01) .There was no relationship between survivin gene expression in colorectal cancers and sex,tumor size,histological types,lymphnode metastasis,distant metastasis and Dukes stage.The expression of VEGF gene in colorectal cancers correlated with distant metastasis and Dukes stage,of which Dukes D was significantly higherthan Dukes A,B.(P<0.01).(2)The PCR products shared 99% of homology (survivin) and 98% (VEGF) with human counterparts. (3) The immunoreactivity of survivin and VEGF increased in the transition from polyp to carcinoma (P<0.05).Similar changes were observed for PCNA LI,MVD(P<0.001,respectively), but not for AI,which decreased from tubular adenoma to carcinoma(P< 0.001).The expression of survivin protein was positively correlated with VEGF (r=0.296,P=0.03),PCNA LI,and MVD(P< 0.001 for both),but inversely correlated with AI (P< 0.001).The expression of VEGF protein was also posively correlated with PCNA LI (P<0.05)and MVD(P<0.001),but not correlated with AI(P> 0.05).Conclusion: (1)Survivin was a special tumor marker and was independent of histopathological characteristics. (2)The expression of survivin was an early event in the development of colorectal cancer. It plays an important role during human colorectal tumorigenesis through not only inhibiting the apoptosis of colorectal adenoma cells and tumor cells but also accelerating their proliferative activity.lt may become a potential early diagnostic marker.(3)The expression of survivin was associated with angiogenesis in the development of colorectal cancer.A potential correlation between survivin and VEGF was Likely in colorectal carcinogenesis.