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 beta 2-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.
Levine
E A
EA
Division of Surgical Oncology, University of Illinois at Chicago 60628.
Holzmayer
T A
TA
Roninson
I B
IB
Das Gupta
T K
TK
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D015996:Survival Rate
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins