Association of cyclin D1, p16 and retinoblastoma protein expressions with prognosis and metastasis of gallbladder carcinoma

Abstract

To investigate the role of cyclin D1, p16 and retinoblastoma in cancerous process of gallbladder carcinomas and to assess the relation between cyclin D1, p16, Rb and the biological characteristics of gallbladder carcinoma. Forty-one gallbladder carcinoma, 7 gallbladder adenoma and 14 chronic cholecystitis specimens were immunohistochemically and histopathologically investigated for the relation of cyclin D1, p16 and Rb with Nevin staging and pathologic grading. The expression rates of abnormal cyclin D1 in gallbladder carcinoma (68.3%) and gallbladder adenoma (57.1%) were significantly higher than those in chronic cholecystitis (7.1%) (P<0.05). No significant difference was found both among the pathological grades G(1), G(2) and G(3) and among Nevin stagings S(1)-S(2), S(3) and S(4)-S(5) of gallbladder carcinoma. The positive rates of p16 (48.8%) and Rb (58.5%) in gallbladder carcinoma were significantly lower compared to those in adenoma (100.0%) and cholecystitis (100.0%) (P<0.05). The positive rates of p16 and Rb in Nevin stagings S(1)-S(2) (80.0% and 90.0%) and S(3) (46.2% and 61.5%) gallbladder carcinomas were significantly higher than those in S(4)-S(5) (33.3% and 38.8%) (P<0.05), and those in pathologic grades G(1) (54.5% and 81.8%) and G(2) (50.0% and 62.5%) gallbladder carcinoma were significantly higher than those in G(3) (28.6% and 35.7%) (P<0.05). The protein expression of p16 and Rb had a negative-correlation in gallbladder carcinoma (r = -0.2993, P<0.05), and this negative-correlation was correlated with Nevin staging (P<0.05). Moreover, the protein expression of p16 and cyclin D1 had a negative-correlation in gallbladder carcinoma (r = -0.9417, P<0.05). Cyclin D1 may play a role in the early stage of gallbladder carcinoma. Mutation of p16 and Rb genes might be correlated with progression of gallbladder carcinoma. Analysis of p16 and Rb can estimate the prognosis of gallbladder carcinoma. Expression of p16 and Rb may be correlated with Nevin staging and pathologic grading in gallbladder carcinoma.