Expression of p53 upregulated modulator of apoptosis (PUMA) and C-myb in gallbladder adenocarcinoma and their pathological significance.

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.