Thioredoxin reductase 1 (TrxR) is a homodimeric selenoenzyme catalyzing thioredoxin (Trx) in an NADPHdependent manner. With regard to carcinogenesis, these redox proteins have been implicated in cell proliferation, transformation and anti-apoptosis. In the present study, using a hamster cholangiocarcinoma (ChC) model, we evaluated the immunohistochemical expression pattern of TrxR in precancerous lesions and ChCs as well as in normal bile ducts. The goal of this study was to determine the potential role and importance of TrxR in cholangiocarcinogenesis. For the ChC model, we obtained liver tissue specimens with dysplastic bile ducts prior to the development of ChC 8 weeks after initiation of the experiment and ChC samples at 27 weeks. The immunohistochemical analysis showed diffuse cytoplasmic overexpression of TrxR in the dysplastic bile duct epithelial cells as well as in cholangiocarcinoma; this was comparable to the negative or weakly positive in normal and type 1 hyperplastic bile ducts. However, TrxR appeared to be considerably down-regulated in the ChCs when compared to the higher expression observed in the dysplastic bile ducts. Therefore, these results suggest that TrxR overexpression followed by down-regulation might be an important event in cholangiocarcinogenesis, especially at early stages including the cellular transformation of candidate bile ducts. Further studies are however required to determine whether TrxR may be a potential target molecule for chemoprevention against cholangiocarcinogenesis. In addition, the molecular mechanism as well as the importance of the loss of TrxR in the development of cholangiocarcinoma, following dysplastic transformation of bile duct cells, also remains to be clarified.
Animals ; Bile Duct Neoplasms/*enzymology/pathology ; Bile Ducts/enzymology/pathology ; Cholangiocarcinoma/*enzymology/pathology ; Cricetinae ; Disease Models, Animal ; Immunohistochemistry ; Mesocricetus ; Precancerous Conditions/*enzymology/pathology ; Thioredoxin Reductase (NADPH)/*biosynthesis

There has been no report for the expression of cyclooxygenase-2 (COX-2) and its clinicopathologic and biologic significance in ampulla of Vater cancer. This study was aimed for the clarification of COX-2 expression and its biologic roles in ampulla of Vater cancer. Fourty-six patients with ampulla of Vater cancer were enrolled and their COX-2 expression and clinicopathologic features were analyzed. The median age of patients was 60 yr and the mean duration of follow-up was 35 months (range: 14-82 months). Immunohistochemical stainings for COX-2, Ki-67, CD34 and TUNEL staining were performed. The immunoreactive COX-2 expression was present in 24 (52.2%) patients of ampulla of Vater cancer and mainly localized in cytosolic and perinuclear region. There was no significant difference in the length of survival between COX-2 postive and negative group (p=0.9420 by Log Rank test). Also, there were no significant differences of proliferation index (p=0.326), apoptotic index (p=0.764) and microvessel density (p=0.135) between COX-2 positive and negative group. Initial pTNM stage (p=0.0028 by Log Rank test) and blood transfusion over 4 pints during operation (p=0.0254 by Log Rank test) were independent prognostic factor in patients with ampulla of Vater cancer. It is suggested that immunoreactivity of COX-2 is not correlated with clinicopathologic and biologic features of ampulla of Vater cancer.
Adult ; Aged ; Ampulla of Vater*/enzymology ; Ampulla of Vater*/pathology ; Common Bile Duct Neoplasms/enzymology* ; Common Bile Duct Neoplasms/pathology* ; Female ; Human ; Immunoenzyme Techniques ; Isoenzymes/metabolism* ; Male ; Middle Aged ; Prostaglandin-Endoperoxide Synthase/metabolism* ; Statistics ; Survival Rate

OBJECTIVETo detect the expression of human telomerase reverse transcriptase (hTERT) protein and mRNA in bile duct carcinomas and the adjacent tissues and to elucidate its role in bile duct carcinogenesis.

METHODSThe expression of hTERT protein and hTERT mRNA in the formalin-fixed paraffin-embedded specimens of 71 cases of bile duct cancers and 39 cases of adjacent tissues was detected by streptavidin-peroxidase immunostaining and in situ hybridization. The correlation was analysed statistically between the expression of hTERT protein and mRNA and clinicopathological parameters bile duct carcinomas.

RESULTSThe positive rate of hTERT protein expression and mRNA expression in malignant specimens was 78.9% (56/71) and 67.6% (48/71), while that in the adjacent tissues was 35.9% (14/39) and 23.1% (9/39), respectively. All the positive signals were found in the hyperplastic biliary epithelia. No significant correlation was established between hTERT expression and clinicopathological parameters.

CONCLUSIONhTERT gene transcription and protein expression is most likely involved in the proliferation and malignant transformation of bile epithelia and the malignant progression of bile duct carcinomas. The detection of hTERT expression may serve elucidating the carcinogenesis of bile duct.

Adult ; Aged ; Aged, 80 and over ; Bile Duct Neoplasms ; enzymology ; pathology ; DNA-Binding Proteins ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; RNA, Messenger ; analysis ; Telomerase ; analysis ; genetics