27113

BBC3

BCL2 binding component 3;BBC3;BCL2 binding component 3

bcl-2-binding component 3|p53 up-regulated modulator of apoptosis

19q13.3-q13.4

protein-coding

BACKGROUND: Gallbladder cancers have a very poor prognosis without specific molecular marker being identified. In this study we studied PUMA, c-Myb and p53 expression in benign and malignant lesions of gallbladder and analyzed their clinicopathological significance. METHOD: Immunohistochemical staining of PUMA, c-Myb and p53 protein was performed in 108 gallbladder adenocarcinomas, 46 peritumoral tissues, 15 polyps, and 35 chronic cholecystitis. RESULTS: We demonstrated that the percent of positive PUMA, c-Myb and p53 expression was significantly higher in gallbladder adenocarcinomas than in peritumoral tissues, polyps and chronic cholecystitis (p < 0.05 or 0.01). Benign gallbladder epithelium with positive PUMA, c-Myb or p53 expression showed moderately or severely atypical hyperplasia. The percent of positive PUMA, c-Myb and p53 expression was significantly higher in the cases having poorly differentiated adenocarcinoma with large tumor mass, lymph node metastasis and high invasiveness than cases with well-differentiated adenocarcinoma with small tumor mass and without metastasis and invasiveness (p < 0.05 or p < 0.01). The percent of positive PUMA, c-Myb and p53 expression was significantly higher in cases with radical resection than without resection (p < 0.05). Univariate Kaplan-Meier analysis showed that PUMA, c-Myb and p53 expression was associated with decreased overall survival (p < 0.05 or p < 0.01). Multivariate Cox regression analysis showed that PUMA, c-Myb or p53 expression was a poor-prognostic predictor in gallbladder adenocarcinoma. CONCLUSION: PUMA, c-Myb and p53 expression closely relates to the carcinogenesis, fast-progression, easy-metastasis, high-invasion, and poor-prognosis in gallbladder adenocarcinoma.

PURPOSE: An increasing number of studies have shown that PUMA and C-myb signaling pathways are involved in various human cancers including colon carcinomas. However, few studies have examined gallbladder cancer specimens, and little is known about the clinical and pathological significance signaling changes may have in gallbladder adenocarcinoma. This study has investigated the expression of PUMA and C-myb in benign and malignant lesions of gallbladder and its pathological significance. METHODS: Tissue specimens from 108 gallbladder adenocarcinoma patients, 46 adjacent tissues, 15 cases of adenomatous polyps, and 35 surgical specimens from chronic cholecystitis patients were routinely paraffin embedded and sectioned. PUMA and C-myb expressions were detected with EnVision immunohistochemistry. RESULTS: Positive rates of PUMA and C-myb are significantly higher in gallbladder adenocarcinoma tissues than that in the other three (P < 0.01). Gallbladder epithelial cells in PUMA and/or C-myb positive benign cases manifest moderate to severe atypical dysplasia. Positive rates of PUMA and C-myb in well-differentiated tumors with maximum diameter of <2 cm and with no lymph node metastasis and invasion of the surrounding tissues are significantly lower than that in those poorly differentiated cases with maximum diameter of >/= 2 cm, lymph node metastasis, and invasion of the surrounding tissues (P < 0.05 or P < 0.01). The postoperative survival of patients whose tumor specimens are positive for PUMA and C-myb is significantly shorter than that of those who are negative for both markers (P < 0.05 or P < 0.01). CONCLUSIONS: Our results have demonstrated that PUMA and C-myb positive gallbladder tumors progress rapidly, are prone to metastasis, possess strong invasive ability, and have poor prognosis.