Multidrug resistance-associated protein expression in clinical gastric carcinoma.

Abstract

We examined the relationship between the expression of a multi-drug resistance-associated protein (MRP) and the biologic factors regarding invasion and metastasis of human gastric cancer. In 75 patients with gastric cancer, the expression of MRP was immunohistochemically investigated and the expression of MRP mRNA was also detected using reverse transcription PCR (RT-PCR). Sensitivity to the anticancer agents, cisplatin (CDDP), doxorubicin (DXR), etoposide (VP-16), and mitomycin C (MMC) was examined using the MTT {3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl[2H]-tetra-zolium bromide} assay. The relation between MRP expression and development, invasion, and metastasis of cancer was analyzed, and overexpression of the tumor suppressor gene p53 was investigated, immunohistochemically. 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 expression and clinicopathologic features or prognosis. Positive p53 staining was evident in 16 of 34 MRP positive tumors (47%) and 18 of 41 negative ones (44%), and there was no significant correlation between MRP and abnormal p53 expression. The MTT assay showed that MRP positive gastric cancer tissue was less sensitive to CDDP, DXR, and MMC compared with MRP negative ones. A similar tendency was noted with VP-16. MRP expression relates to the chemosensitivity of tumor cells against some anticancer drugs and is independent of known factors related to the development, invasion, and metastasis of human gastric cancers.