Study On The Expression And Clinical Significance Of MMAC1/Pten Gene In Cholangiocarcinoma

Objective: The MMAC1/MMAC1/Pten gene is the first tumor suppressor encoding a phosphatase identified by far, whose mutation is found in multiple rumors. However, the clinical significance of this gene in cholangiocarcinoma remains unclear. So the purpose of our research aims to investigate the expression of MMAC1/ Pten gene in cholangiocarcinoma and its clinical significance.Methods: Tissue samples were taken from 32 patients with cholangiocartinorna and 5 adenoma of gallbladder , fixed in formaldehyde and embedded with paraffin . 5 samples from normal bile duct tissues were also withdrawn. Protein and gene expression of MMAC1/ Pten were analyzed by irnmunohistochemistry and in situ hybridzation . Cholangiocarcinoma cell line Q939 was determined for the expression of MMAC 1/ Pten as well.Results: MMAC1/ Pten protein and mRNA expression were positive not only in all 5 samples of normal bile duct tissues (5/5, 100% ), but also in all 5 cases of adenoma of gallbladder (5/5,100%).Of the 32 cases of cholangiocarcinoma, MMAC1/ Pten protein expression were positive in 20 cases (64.00%), the positive staining was seen in the cytoplasm; there was no positive staining in cholangiocarcinoma cell line Q939.73.6% of 32 cases of cholangiocarcinoma were MMAC1/ Pten mRNA positive, and MMAC1/ Pten mRNA was clearly observed in the cytoplasm of cholangiocarcinoma cells. No expression of MMAC1/ Pten mRNA was foundin cholangiocarcinoma cell line Q939 either.Compared with normal bile duct tissue, the negative expression rates of MMAC1/ Pten mRNA and protein in cholangiocarcinoma were higher.There was no correlation between the protein and mRNA expression of MMAC1/ Pten and such factors as sex, age in cholangiocarcinoma , but a significant correlation between the expression of MMAC1/ Pten and the differentiation, metastasis and postoperative prognosis were found. The less the MMAC1/ Pten protein and mRNA were, the poorer the differentiation and prognosis were. The positive rates of MMAC1/ Pten protein and mRNA expression in well differentiated adenocarcinoma were significantly higher than those in poorly differentiated adenocarcinoma (P<0.01), 40% vs50% and 72.73% vs 86.36% respectively. The levels of MMAC1/ Pten protein and mRNA in patients with metastasis were significantly higher than in those without metastasis.Conclusions: Inactivation of MMAC1/ Pten gene may play an important role in the pathogenesis of cholangiocarcinoma. The positive expression of both protein and mRNA of MMAC1/ Pten may be related with favorable prognosis of cholangiocarcinoma.