The human multidrug resistance gene (MDR-1): Immunocytochemical detection of its expression in oral SCC

A large number of oral cancer patients show poor or partial response to che motherapy and the mechanisms ale poorly understood. At present, an MDR-I pr oduct, the P-170 glycoprotein, is the best known of the P-170 family and is involved in resistance to natural product-based chemotherapeutics, includi ng taxanes, anthracyclines, vinca alkaloids, podophyllotoxins and camptothe cins. Although several reports suggest that P-170 is clinically relevant in haematological malignancies, its role in solid tumours is not well underst ood. Its overexpression has been found to be correlated with the poor outco me observed in patients treated with chemotherapy and presenting drug I res istance. The aim of this study was to detect the protein expression pattern s of MDR-I product by immunohistochemistry in formalin-fixed-paraffin-embed ded tissues. For these reasons, 30 oral SCC and 6 healthy oral mucosa speci mens were tested with anti-P-170 antibodies using standard streptavidin-bio tin-peroxide technique. Immunohistochemistry demonstrated that 4 cases (66. 6%) of normal oral mucosa and 24 cases (80%) of oral SCC showed positivity. Four cases (13.4%) showed strong positivity in tumour areas and complete n egativity in normal epithelial cells adjacent to the tumour. No staining wa s observed in stromal structures, with the exception of the lymphocytic com partment that showed a strong staining as reported in literature for CD56and CD8+ cells. Four GI tumours (33%) and 2 G3 tumour (33%) showed strong p ositivity in areas with a higher degree of differentiation. P-170 positivit y in normal epithelial cells of smoker patients, in differentiated area of neoplasia and negativity or zonal positivity in undifferentiated area of tu mour suggested that activation of the MDR-I gene or selection of intrinsica lly multidrug resistance neoplastic cells may occur at early stages of tumo rigenesis of oral cancers, before the real evidence of cellular transformat ion. Thus the contact with possible chemical carcinogens, such as those of tobacco smoke, may induce activation of MDR-I gene. This study was conducte d only on untreated carcinomas so for this reason it cannot indicate the re al incidence of acquired multidrug resistance. The data of MDR-I product ex pression by immunohistochemistry in oral SCC might suggest that an overexpr ession of this protein could constitute a hallmark of potential more aggres sive phenotype for this type of neoplasia and a rapid method for pre-screen ing tumours for a constitutive multidrug resistance in order to orientate t he cancer treatment.