Expression Of Survivin And Its Relationship To Caspase-3,Cyclin D1,ki-67 Labeling Index And Microvessel Density In Colorectal Carcinoma

Background and aims: A balance between cell proliferation and apoptosis is crucial for normal development and tissue-size homeostasis. Disturbance of this balance will lead to neoplastic transformation and progression. Recently, a newly identified inhibitor of apoptosis, survivin, was found to be expressed in fetal tissue and in many cancers but not in normal adult tissues. It directly inhibits cysteinyl aspartate-specific proteinase-3 and -7(caspase-3 and -7) activity, regulates the cell cycle in the G2/M phase, and is related to cell proliferation and angiogenesis. Caspase-3 is a key effector protein in the apoptosis protease cascade. Cyclin D1 is a member of cell cycle regulating protein and plays an important role in the check point of G1/S phase, and its overexpression can accelerate the translation from G1 to S phase and cell proliferation. The Ki-67 labeling index (ki-67 LI) can give a good indication of the cell proliferating activity and can be used as an objective marker of cell proliferation. Microvessel density (MVD) is usually used to reflect the activity and inclination of angiogenesis in tumor and gives valuable reference in estimating tumor's development, metastasis and prognosis. CD31 is a maker of vessel endothelial cell which marks the microvessel well in tumor tissue. Colorectal carcinoma is one of the common digestive carcinomas, as other tumors, the mechanism of colorectal carcinogenesis has not been cleared.In this study, We sought to investigate the expression of survivin mRNA and survivin, caspase-3, cyclin Dl, ki-67, CD31 protein in colorectal carcinoma, and to identify the clinical significance of survivin and its relationship with the expression ofcaspase-3, cyclin D1, ki-67 LI and MVD in colorectal carcinoma, so that provide theoretical basis for early diagnosis and therapy of colorectal carcinoma. Materials and Methods: (1) Tissue specimens used for this study were obtained from 86 patients, which were resected surgically or endoscopically at Henan Provincial Peoples Hospital and Henan Provincial Tumor Hospital from Jan.2003 to Oct.2003. Tissue specimens were stored at -70 C until needed. All the samples including 12 normal colorectal mucosae, 28 adenomas and 46 carcinomas were fixed in 4% Polyoxymethylene/ 0.1M PBS (0.1%DEPC) and embedded in paraffin. (2) The expression of survivin mRNA was detected by in situ hybridization and the expression of survivin, caspase-3, cyclin Dl, ki-67, CD31 protein were detected by the standard streptavidin-peroxidase (SP) technique. (3) The statistical software package SPSS 10.0 was used. A two-tailed P- value less than 0.05 was considered to indicate statistical significance.Results: (1) The positive rates of survivin mRNA and protein expression in normal colorectal mucosae, adenomas and carcinomas were 0%, 21.4%, 67.4%; 0%, 14.3%, 65.2%; respectively. Expression of survivin mRNA and protein were higher in colorectal carcinoma than in normal colorectal mucosae and adenomas (P <0.01), there was no difference in normal colorectal mucosae and adenomas (P >0.05). An 89.1% concordance between survivin mRNA expression and survivin protein was noted in 46 tumors, there was a correlation between survivin mRNA and survivin protein expression (P <0.001).(2) The positive rates of caspase-3 expression in normal colorectal mucosae, adenomas and carcinomas were 25%, 75%, 60.9%; respectively. The expression of caspase-3 in adenomas and carcinomas was significantly higher than in normal mucosae (P <0.05). The expression of caspase-3 in colorectal adenomas was higher than in carcinomas, but the difference has no statistics significance (P >0.05). The positive rates of caspase-3 were higher in well differentiated than in poorly differentiated colorectal carcinomas (P <0.01).(3) The positive rates of cyclin D1 expression in normal colorectal mucosae, adenomas and carcinomas were 8.3%, 25%, 58.7%; respectively. Expressions ofcyclin Dl were higher in colorectal carcinomas than in normal colorectal mucosae and adenomas (P <0.01). The expression of c...