Changes in P-glycoprotein expression in gastric carcinoma with respect to distant gastric mucosa may be influenced by p53.

Abstract

The effectiveness of some chemotherapeutic agents used to treat gastric carcinoma patients may be impaired by the presence of P-glycoprotein (P-gp) and the status of p53. A modulation of P-gp expression by p53 or other alterations during tumorigenesis have been reported. The authors analyzed P-gp expression in relation to p53 and histopathologic features in gastric carcinoma. Forty-one resected gastric carcinomas and mucosa distant from the tumor were assessed for P-gp expression by immunohistochemistry with C494 and JSB-1 antibodies. p53 expression was also immunohistochemically assessed by DO7 antibody in tumor samples. P-gp and p53 expression were semiquantitatively analyzed according to the percentage of stained cells. Histologic type, grade, vessel invasion, and stage were also studied. Moderate or high P-gp expression was detected in gastric carcinoma in 29 cases (71%) and in gastric mucosa remote from the tumor in 36 cases (88%). This reduction in P-gp expression was observed in 22% of the carcinomas, all but 1 being p53 immunonegative tumors. Thus, 8 (42%) of the p53 immunonegative carcinomas showed a loss of P-gp expression compared with their distant gastric mucosa. All p53 immunopositive carcinomas coexpressed P-gp. No correlation between P-gp expression and histologic type, grade, vessel invasion, or stage was found. P-gp expression in gastric carcinomas is frequent and coexpression with p53 is found. The analysis of P-gp expression in carcinomas and distant mucosa show that it is not regulated by p53, but a loss of P-gp detected in some of these carcinomas is mainly associated with a lack of p53 protein accumulation.