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MDR-1 expression in metastatic malignant melanoma
E A Levine1, T A Holzmayer, I B Roninson
1Division of Surgical Oncology, University of Illinois at Chicago 60628.
The Journal of Surgical Research
|June 1, 1993
Summary
Metastatic malignant melanoma (MMM) often resists chemotherapy due to multidrug resistance (MDR). This study found low-level MDR-1 gene expression in 45% of MMM tumors using a sensitive PCR assay, suggesting non-MDR mechanisms are more dominant.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Metastatic malignant melanoma (MMM) has a poor prognosis, partly due to resistance to chemotherapy.
- Multidrug resistance (MDR), mediated by the MDR-1 gene, is a known mechanism of chemotherapy resistance.
- Previous studies using immunohistochemistry failed to detect MDR-1 expression in MMM.
Purpose of the Study:
- To evaluate the incidence of MDR-1 gene expression in MMM.
- To utilize a highly sensitive polymerase chain reaction (PCR)-based assay for accurate detection.
- To correlate MDR-1 expression with clinical parameters and survival outcomes.
Main Methods:
- Analysis of 22 snap-frozen MMM specimens.
- RNA extraction, cDNA synthesis, and coamplification of MDR-1 and beta 2-microglobulin using PCR.
- Quantification of MDR-1 PCR product relative to known expression standards.
Main Results:
- MDR-1 expression was detected at low levels in 45% of MMM specimens.
- No MMM tumors exhibited high levels of MDR-1 expression.
- No significant correlation was found between MDR-1 expression and overall survival, disease-free survival, tumor thickness, histology, or sex.
Conclusions:
- MDR-1 is frequently expressed at low levels in metastatic malignant melanoma.
- The observed low-level MDR-1 expression suggests that non-MDR mechanisms play a dominant role in chemotherapy resistance in MMM.
- Further research is needed to ascertain the clinical significance of MDR-1 expression in MMM.