Expression And Significance Of P27 And CyclinE In Gallbladder Carcinoma

Background and objective Gallbladder carcinoma is one of the most popular malignant tumor in bile duct system. The prognosis of gallbladder carcinoma is very poor. Operation is the main treatment of gallbladder carcinoma. Histopathological stage is still the most popular 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. Abnormal control on cell cycle, especially the abnorm of the check point of G1/S stage, plays an important role in carcinogenesis.. P27 is an important CDK inhibitor, which binds to and inhibits preferentially G1-phase kinases thereby arresting the cell cycle at G1-phase. Proto-oncogene cyclinE, encodes cyclinE protein,which acts as an important positive regulator in G1/S transition,and appears to be closely linked with carcinogenesis. CyclinE,as an oncogene and p27, as an antioncogene modulate the growth and diferentiation of cells by working on the cell cycle check point of G1/S stage, role in carcinogenesis. The researches on oncogene, antioncogene and the role of cell cycle control have great significance to help us treat tumor. This research, by studying the expressions of cyclinE and p27 in the tissues of gallbladder carcinomas (GBC), was to explore the correlation of cyclinE and p27 and gallbladder carcinogenesis,the histological grade, nevin′s stage, depth of invasion, and hence evaluate their roles in carcinogenesis and their significance at clinic.Methods The samples from 40 patients with gallbladder carcinoma, who underwent surgical resection at The First Afiliated Hosptial of Anhui Medical University and Lu'An Peaple's Hospital from 2001 Jan to 2006 Dec, were used for this study. 20 chronic cholecystitis (CC) specimens were control group. The samples were routinely fixed in 10% formalin and embedded in paraffin. After sectioned into slices, we detected the expression of p27 and cyclinE protein by immunohistochemical staining technique(SP method). We analyzed the relationship between the expression of p27 and cyclinE protein with clinical parameters.Results (1)The positive expression rate of p27 in gallbladder carcinoma was 45.0%(18/40), which was lower than that in chronic cholecystitis(100% ), P<0.05. The positive expression rate of cyclinE in gallbladder carcinoma was 67.5%(27/40), which was significantly higher than that in chronic cholecystitis(15.0%,3/20), P<0.05. (2)The expression level of p27 protein in gallbladder carcinomas showed an obvious difference in the histological grade, nevin′s stage, depth of invasion, lymph node metastasis, infiltration (P<0.05). But not markedly associated with patient′s age, , histological types, tumor size. The expression level of cyclinE protein in gallbladder carcinomas showed an obvious difference in the histological grade,nevin′s stage, depth of invasion (P<0.05). But not markedly associated with patient′s age, histological types, tumor size, lymph node metastasis, infiltration. Log rank test showed that the p27 and cyclinE expression were significantly related with prognosis of the patients (P<0.05).(3)There was negative correlation between p27 and cyclinE expression (r=-0.375,P<0.05).Conclusion The decreased expression of p27 and the high expression of cyclin E result in abnomal regulation of cell cycle,which may be associated with gallbladder carcinogenesis and progression.