Clinical relationship between MDR1 gene and gallbladder cancer.

BACKGROUND: The most common mechanisms of multidrug resistance (MDR) in cancer cells is the expression of an energy-dependent exfflux pump. P-glycoprotein (P-gp) encoded by MDR1 gene and multidrug associated protein (MRP) are well known proteins associated with MDR. In human cancers, the MDR1 gene expression is common in patients with intrinsic and acquired MDR. It is a major therapeutic problem in cancer chemotherapy. Previously we found that the MDR of HCC is related to MRP gene expression and initiates the intrinsic MDR. The aim of this study is to study the expression of MDR1 gene encoding P-gp and MDRl mRNA in primary gallbladder carcinoma, and analyze its clinical significance. METHODS: Immunohistochemistry (IHC) S-P method and in situ polymerase chain reaction (ISPCR) were used to detect the expression of P-gp and MDR1 mRNA in 53 cases of untreated primary gallbladder carcinoma and 12 cases of cholecystitis (archival paraffin-embedded tissues). RESULTS: The positive expression rates of P-gp and MDR1 mRNA in the 53 cases and 12 cases were 60.38%, 71.69% and 25.00%, 33.33%, respectively. There was a significant difference between the two groups (P<0.05). The positive expression rate of P-gp and MDR1mRNA were 69.44%, 83.33% and 41.18%, 47.06% respectively in tissues in stage of Nevin I-III against Nevin IV, V (P<0.05). In well, moderately differentiated gallbladder carcinoma tissues, their expressions were 79.49%, 69.23% against 50.00%, 35.71% in low, undifferentiated tissues (P<0.05). CONCLUSIONS: MDR to gallbladder carcinoma is closely related to the intrinsic MDR and it provides an important evidence to reverse the MDR by detection of the MDR1 gene. Meanwhile, MDR1 gene expression in gallbladder carcinoma is correlated with some biological characteristics, takes part in the carcinogenesis of gallbladder tissues, and acts as a valuable biomarker of prognosis.

Clinical significance of mrp gene in primary hepatocellular carcinoma.

OBJECTIVE: To study the relations among the expression of the multidrug resistance associated-protein (mrp) gene and clinicopathologic features, the influence of alpha-fetoprotein (AFP), and prognosis of patients who received adjuvant chemotherapy after resection of primary hepatocellular carcinoma (HCC). METHODS: The expression of the mrp gene encoding MRP and mRNAmrp was determined in tissues from 54 untreated patients with HCC, adjacent tissues from 24 patients with HCC and archival paraffin-embedded tissues from 12 patients with posthepatic cirrhosis. The relationship between the mrp gene expression and the change level of AFP was analyzed in the 24 postoperative HCC patients whose AFP level was measured after 2 weeks. All of the HCC patients were followed up. RESULTS: The percentage of positive expressions of MRP and mRNAmrp in the three kinds of tissues was 57.40%, 25.00%, 16.67%, and 72.22%, 37.50%, 33.33% respectively. Significant difference was noted in the untreated HCC tissue, compared to the other two tissues (P<0.05). No difference existed between the mrp gene expression and such clinicopathologic findings, as age, sex, and tumor size (P> 0.05), but the expression was related to the degree of differentiation of HCC (P<0.05). The effective rate of AFP in the mrp gene positive expression group or postoperative chemotherapeutic patients was lower than that in the negative group (P<0.05). Although no difference was seen in the 1-, 3-, 5-year survival rates of HCC patients (P>0.05), the mean survival time of postoperative HCC patients or the negative mrp gene expression group was longer than that of the positive group (P<0.05). CONCLUSIONS: Multidrug resistance (MDR) of HCC is related to mrp gene expression and initiates the intrinsic MDR. Detection of mrp gene expression is of great significance in accessing chemotherapeutic resistance of HCC, which provides evidence for reversing MDR in HCC. The mrp gene may be a useful marker in detecting prognosis of HCC patients because its expression is correlated with tumor differention and mean survival time of the patients.

[Expression and implication of multidrug resistance associated -protein gene in primary hepatocellular carcinoma].

OBJECTIVES: To investigate the relationship between the expression of mrp and both the responses to chemotherapy and the level of alpha-fetoprotein (AFP). METHODS: S-P immunohistochemical staining and in situ PCR were adopted to detect MRP and mRNA mrp in 54 cancer tissues taken from untreated HCC patients whose tumor could not be removed during the operation, 24 para-cancer tissues, and 12 posthepatitis cirrhosis paraffin-embedded tissues. The relationship between the expression of mrp and their curative effect to chemotherapy in all the patients was analyzed, so was the relationship between the expression of mrp and the level of AFP in 38 patients whose AFP was positive after operation. RESULTS: The positive rates of expressing MRP and mRNA mrp in the three kinds of tissues were 61.1%, 25.0%, 33.3% and 77.8%, 37.5%, 41.7%, respectively, with higher rates in HCC tissues than those in other tissues (chi2=9.842, P< 0.01; chi2=13.956, P<0.01). The rates of curative effect to chemotherapy in groups of negative and positive MRP and mRNA mrp expression were 61.9%, 30.3% and 75.0%, 33.3%, respectively, with significant difference between the negative and positive groups (chi2=5.242, P<0.05; chi2=6.627, P< 0.05). As the same as the percentage of curative effect to chemotherapy, the rates of AFP level decreased evidently were 62.5%, 27.3% and 87.5%, 30.0%, with remarkable difference between the two groups (chi2=4.710, P<0.05; chi2=8.566, P<0.05). CONCLUSIONS: The multidrug resistance (MDR) of HCC is related to mrp expression, which initiates the intrinsic MDR. There is an important significance by detecting mrp expression in selecting chemotherapeutic method, and the expression of mrp can act as an indicator for chemotherapeutic sensitivity in HCC patients.