| Gallbladder carcinoma is the most popular malignant tumor in bile duct system. The prognosis is very poor and main treatment is operation. Histopathological stage is still the most important indexes to predict patient' s prognosis. However, tumor stage may lead physician to a wrong way sometimes because of the biological heterogeneity of tumor. Recent studies have revealed that uncontrolled cell cycle is very important to uncontrolled cell proliferation and carcinogenesis. Cyclin-dependent kinase(CDK), together with cylin and CDK inhibitor,govern cell cycle progression in eukaryotic cell.In cell cycle .different phase is regulated by different factors, in them, Gi-phase regulators are most closely related to carcinogenesis. P27 is an important CDK inhibitor recently, which binds to and inhibits preferentially Gi-phase kinases thereby arresting the cell cycle at Gi-phase. Decreased P27 expression has been shown to associated with the development and malignant progression in many human malignant tumors,and providesindependent prognostic information.Proto-oncogene cyclin Di encodes cyclin Di protein .which acts as an important positive regulator in d/S transition , and appears to be closely linked with carcinogenesis , the overexpression of cyclin Di have been reported in a variety of malignant tumors.Here we evaluated the expression of the cell cycle-related prteins cyclin Di and P27 in surgically resected gallballder carcinoma using immunohistochemical En Vision method. The relationship of clinicopathological characteristics and prognosis of gallbladder carcinoma with expression of cyclin Di and p27 was analyzed.Material and MethodsPatients: Paraffin embedded specimens from 51 patients who underwent operation for gallbladder carcinoma in the Run Run Shaw hospital of Zhejiang University medical college from 1994 to 2000 were selected for this experiment. There were 19 male in total 51 cases and 32 female. The mean age was 64. 1(31~82). The operation types were: simple cholecystectomy 13 cases; radical cholecystecomy 17 cases; extended radical cholecystectomy 2 cases;palliative cholecystectomy 19 cases. The clinicopathological stage was determined obeying the UICC standard:4 cases for stage I ;10 cases for stage II ; 11 cases for stage HI and 26 cases for stage IV. And we took 12 cases of adenoma of gallbladder and 10 cases of chronic6cholecystitis specimens for the comparison.Follow-up: All cases were followed up by phone or by interview. 49 cases had got complete prognostic data, 20 cases survived more than 1 year after operation all other patient died in 1 year because of tumor.1-year survival rate is 40.8%.Expression of cyclin Di and p27 were detected in 51 cases by imraunohistochemical En Vision method,with 1:50 dilution of primary antibody of cyclin Di and p27 .positive and negative controls were designed. Judging and grading system :for each antibody, positive immunostaining appears as yellow brown nucleus with clear background. According to a widely accepted criterion,tumors that expressed strong immunoreactivity in >5% of the cells were considered cyclin Di and p27 positive. Statistical analysis: All data was processed with SPSS 10.0 software bag on personal computer. Enumeration data checked by Chi-Squre test and Fisher' s exact test, Multiple Factors Regression Analysis employed Cox model.Result and DiscussionP27 expression was observed in 17/51 gallbladder carcinoma (33. 3%), which was significantly lower than in chronic cholecystits,the difference was very significant(P<0.05); The expression of p27 was not associated with sex, age and histologic subtype (P>0. 05) ;p27 positivity in lymph node positive group was significantly lower than in lymph node negative group(P<0.05);7The expression of p27 was also associated with clinical TNM stage (FVvs I , P<0. 01 ;UI vs I , P<0. 05) . These data indicate that decreased P27 expression is involved in the development and progression of gallbladder carcinoma, and suggestive of poor prognosis.Cyclin Di expressio...
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