Abstract: Background and purpose: Primary carcinoma of the gallbladder (PCG) is a malignant tumor with extremely high mortality, and the mechanism of its malignant transformation is not yet clear. Previous studies found abnormal expression of p57^KIP2 in a variety of human malignant tumors. This study aimed to analyze the expressions of p57^KIP2, cyclin D1 and cyclin E in PCG and their clinical significances. Methods: The mRNA expression and protein levels of p57^KIP2, cyclin D1 and cyclin E in 60 cases of PCG, 20 cases of adenoma of the gallbladder (AG) and 20 cases of chronic cholecystitis (CC) were detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and immunohistochemistry, respectively. Results: The mRNA expression and protein levels of p57^KIP2 in PCG, AG and CC increased gradually, and there were significant differences among the three groups (P<0.05). The mRNA expression and protein levels of cyclin D1 and cyclin E in PCG, AG and CC decreased gradually. The difference between PCG and AG, or between PCG and CC was statistically significant. In PCG tissues, the protein expression of p57^KIP2 was associated with clinical stage, histological grade and node metastasis (P<0.05). The protein level of cyclin D1 was associated with clinical stage (P<0.05). There was a negative correlation between the expressions of p57^KIP2 and cyclin D1, or p57^KIP2 and cyclin E. However, the correlation between cyclin D1 and cyclin E expressions was positive (P<0.05). Conclusion: Reduced level of p57^KIP2 and overexpression of cyclin E may be one of the mechanisms underlying carcinogenesis of PCG. p57^KIP2, cyclin D1 and cyclin E were independent prognostic factors for PCG.

Key words: Primary carcinoma of the gallbladder, p57^KIP2, Cyclin D1, Cyclin E, Real-time fluorescence quantitative polymerase chain reaction, Immunohistochemistry