MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN EXPRESSION IN CLINICAL GASTRIC-CARCINOMA

BACKGROUND. We examined the relationship between the expression of a m ultidrug resistance-associated protein (MRP) and the biologic factors regarding invasion and metastasis of human gastric cancer. METHODS. In 75 patients with gastric cancer, the expression of MRP was immunohist ochemically investigated and the expression of MRP mRNA was also detec ted using reverse transcription PCR (RT-PCR). Sensitivity to the antic ancer agents, cisplatin (CDDP), doxorubicin (DXR), etoposide (VP-16), and mitomycin C (MMC) was examined using the MTT dimethyl-2-thiazolyl) -2,5-diphenyl[2H]-tetrazolium bromide} assay. The relation between MRP expression and development, invasion, and metastasis of cancer was an alyzed, and overexpression of the tumor suppressor gene p53 was invest igated, immunohistochemically. RESULTS. Immunohistochemically detected MRP positive tumors were noted in 34 of 75 excised tumors (45%), and confirmed by RT-PCR. There was no significant relation between MRP exp ression and clinicopathologic features or prognosis. Positive p53 stai ning was evident in 16 of 34 MRP positive tumors (47%) and 18 of 41 ne gative ones (44%), and there was no significant correlation between MR P and abnormal p53 expression. The MTT assay showed that MRP positive gastric cancer tissue was less sensitive to CDDP, DXR, and MMC compare d with MRP negative ones. A similar tendency was noted with VP-16. CON CLUSIONS. MRP expression relates to the chemosensitivity of tumor cell s against some anticancer drugs and is independent of known factors re lated to the development, invasion, and metastasis of human gastric ca ncers. (C) 1996 American Cancer Society.