P-glycoprotein, metallothionein and NM23 protein expressions in breast carcinoma

Cellular drug resistance and increased metastatic potential are the major o bstacles in the successful treatment of cancer with chemotherapy. The aim o f this study was to investigate whether the immunohistochemical expression of two proteins implicated in drug resistance (P-glycoprotein and metalloth ionein) and the product of the suppressor gene nm23 could be related to pro gnosis in breast cancer. Seventy-two patients with palpable or occult breast carcinoma, not treated with chemotherapy or endocrine therapy, were examined. Immunohistochemical methods were used to determine the expression of P-glycoprotein (PG), metal lothionein (MT), nm23, as well as the estrogen receptor (ER), the p53 statu s, and the Ki67 index. The results were correlated with clinical and morpho logical features. Cytoplasmic and membrane-specific immunostainings of PG w ere seen exclusively in tumor cells and identified in 14 of 72 cases (19.4% ). Only a statistically significant association with metastases, (p = 0.06) and recurrences (p = 0.1) was observed. MT positive reaction was identifie d in the cytoplasm of the tumor cells in 47 (65.3%) cases. Statistical sign ificance was associated with metastases (p = 0.07), but not with death or r ecurrences. Specific immunostaining of nm23 protein was seen only in the cy toplasm of tumor cells. A positive reaction was observed in 55 of 72 (89.3% ) cases. Although a significant association between nm23 protein expression and other morphologic and immunohistochemical variables did not exist, we observed a higher morbidity in patients with the MT-positive/nm23-negative tumor phenotype. Univariate analysis for survival selected the following va riables: histologic grade (p = 0.001), ER (p = 0.002), mitotic index (p = 0 .005), Ki 67 index (p = 0.068), MT (p = 0.046) and PG (p = 0.085). The Cox model provided the following independent variables: histologic grade (p = 0 .021) and metallothionein (p = 0.03). These data confirm the prognosis obse rved in patients with PG or metallothionein expression as well as the indep endence of these two variables. It also suggests that nm23 is not necessari ly involved in the development of an invasive phenotype.