Immunohistochemical study of PUMA, c-Myb and p53 expression in the benign and malignant lesions of gallbladder and their clinicopathological significances.

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.

Expression of CDC6 and GDF-9 and their clinicopathological significances in benign and malignant lesions of the gallbladder.

PURPOSE: Gallbladder cancers are cancers with high disease-specific mortality rates due to the lack of early diagnosis and effective therapy. In this study, we evaluated whether CDC6 and GDF-9 could be a marker for early diagnosis and target therapy. METHODS: CDC6 and GDF-9 expressions in 108 gallbladder adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues were detected using immunohistochemistry (IHC). RESULTS: We demonstrated that positive CDC6 and GDF-9 expressions were significantly higher in adenocarcinomas than that in peritumoral tissues, polyps, and chronic cholecystitis (p < 0.01). Benign lesions with positive CDC6 and negative GDF-9 expression showed moderately- or severely-atypical hyperplasia. The positive rates of CDC6 were significantly lower in cases with well-differentiated adenocarcinoma, small tumor mass, no metastasis of the lymph node, and no invasion of regional tissues (p < 0.05 or p < 0.01). In contrast, GDF-9 expression was significantly lower in the cases with poorly-differentiated adenocaarcinoma, lymph node metastasis, and invasion (p < 0.05 or p < 0.01). Univariate Kaplan-Meier analysis showed that CDC6 (p=0.046) or GDF-9 (p=0.032) expression was associated with decreased overall survival. Multivariate Cox regression analysis showed that increased expression of CDC6 (p=0.042) or decreased expression of GDF-9 (p=0.031) was an independent poor-prognostic predictor in gallbladder adenocarcinoma. CONCLUSION: CDC6 and GDF-9 might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma. The positive expression of CDC6 and negative expression of GDF-9 have poor-prognosis in gallbladder carcinoma.

Immunohistochemical study of Dicer and Drosha expression in the benign and malignant lesions of gallbladder and their clinicopathological significances.

Dicer and Drosha are two key enzymes that are involved in the processing of miRNA production. Their expressions in gallbladder cancer have not been investigated. In this study, we studied Dicer and Drosha expression in 21 non-dysplastic gallbladder epithelia and 108 gallbladder adenocarcinomas by immunohistochemical staining. The clinicopathological significance of Dicer and Drosha expressions was analyzed. We demonstrated that the percent of positive Dicer or Drosha expression was significantly lower in gallbladder adenocarcinoma than that in non-dysplastic gallbladder epithelia (p<0.01). The percent of positive Dicer and Drosha expression was significantly lower in poorly differentiated adenocarcinoma with lymph node metastasis, invasiveness, and no resection than in well-differentiated adenocarcinoma without metastasis, invasiveness, and with radical resection (p<0.05 or p<0.01). Univariate Kaplan-Meier analysis showed that loss of Dicer and Drosha expression was associated with decreased overall survival (p<0.05 or p<0.01). Multivariate Cox regression analysis showed that loss of Dicer and Drosha expression was an independent poor-prognostic predictor in patients with gallbladder adenocarcinoma. In conclusion, loss of Dicer and Drosha expression is closely related to the metastasis, invasion, and poor-prognosis in gallbladder adenocarcinoma.