MDR-1 Expression in Metastatic Malignant Melanoma

Metastatic malignant melanoma (MMM) carries an ominous prognosis. This poor prognosis is due in part to the remarkable resistance of MMM to a wide variety of antineoplastic agents. One common mechanism of resistance to chemotherapy is that of multidrug resistance (MDR) which is mediated by the MDR-1 gene. Previous efforts to determine MDR-1 expression in MMM have all failed to show expression using relatively insensitive immunohistochemical techniques. The purpose of this study is to evaluate the incidence of MDR-1 expression in MMM using a highly sensitive polymerase chain reaction (PCR)-based assay. Twenty-two clinical snap-frozen MMM specimens were analyzed. Total cellular RNA was extracted and quantitated from which cDNA was synthesized. Sequences of MDR-1 and β2-microglobulin (internal control) cDNA were coamplified using PCR. The relative yield of the MDR-1-specific PCR product was quantitated relative to that of a standard series of cell lines with known MDR-1 expression. Analysis revealed that 45% of MMM expressed MDR-1 at low levels. None of the tumors expressed high levels of MDR-1. Overall survival, disease-free survival, thickness of primary lesion, histology, and sex were not found to correlate with MDR-1 expression. We conclude that MDR-1 is frequently expressed at low levels in MMM. However, this incidence of MDR-1 expression suggests that non-MDR mechanisms of drug resistance are dominant in MMM. Further studies will be required to determine if MDR-1 expression is of clinical significance in MMM.