Study On The Correlation Between Mutant P53 And The Drug Resistant Proteins Pgp And GST-pi In Colorectal Adenocarcinoma

Objective:A large number of papers have indicated that the expression of mutant tumor suppressor gene P53, Pgp and GST-pi is closely related to multidrug resistance in colorectal cancer. Interestingly, recent articles proved that P53 mutation correlated with drug resistant proteins Pgp and GST-pi in molecular level, on the one hand, mutant p53-281 cooperates with ETS selectively up-regulates human MDR1, on the other hand, p53 has a combining site with GSTP1, and p53 transcriptionally regulate GSTP1 expression. Accordingly, we presumed that there is a certain association between mutant p53 and the multidrug resistant proteins Pgp and GST-pi expression in colorectal cancer. The study was to analyze the expression of mutant p53, Pgp and GST-pi in colorectal cancer and the association between them in clinical tissue level, so as to provide clinical basis for further study on the moleculor mechanism of mutant p53 regulates multidrug resistance in colorectal cancer.Methods:By immunochemical ABC techenique, we detected the expression of mutant p53, Pgp and GST-pi in the pathological paraffin tissue of colorectal adenocarcinoma and analyzed the association between them. Among them, there were 44 cases of well differentiated adenocarcinoma,328 cases of moderately differentiated adenocarcinoma, and 32 cases of poorly differentiated adenocarcinoma.Results:●The expression of mutant p53 was mainly in cell nucleus, and positive rate was 34.4%(139/404). The expression of mutant p53 was significantly associated with histological differentiation degree and AJCC staging (P< 0.05).●The expression of Pgp was mainly in membrane, and positive rate was 53.7%(217/404). The expression of Pgp in male was obviously higher than in female, and higher in left colon and rectum than in right colon (P< 0.05).●The expression of GST-pi was primarily in cytoplasm, and its positive rate was 47.8%(193/404). The expression of GST-pi was higher in poorly and moderately differentiated adenocarcinoma cancer than in well d differentiated adenocarcinoma (P<0.05).●The positive percentage of drug resistant proteins Pgp and GST-pi expression was all significantly higher in mutant p53 positive group than mutant p53 negative cases in colorectal adenocarcinoma (P<0.05).Conclusions:Mutant p53 is significantly correlated with overexpression of drug resistantproteins Pgp and GST-pi in colorectal adenocarcinoma. This suggests mutantp53 may participate in regulation on the expression of Pgp and GST-pi.