Reverse Transcriptase-Polymerase Chain Reaction Amplification of MDR1 Gene Expression in Adult Soft Tissue Sarcomas

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Abstract
Expression of the multidrug resistance gene MDR1 is reported to be an important determinant of the response to chemotherapy and survival in some cancers. We compared three methods for determining the intrinsic MDR1 expression in soft tissue sarcomas. We studied MDR1 gene expression in 39 samples from 33 cases of soft tissue sarcomas comprising 11 liposarcomas, nine malignant fibrous histiocytomas, six leiomyosarcomas, four malignant schwannomas, three fibrosarcomas, three synovial sarcomas, and three epithelioid sarcomas, and seven cases of benign soft tissue tumors in adult patients. To detect MDR1 mRNA, reverse transcriptase-polymerase chain reaction (RT-PCR) was performed in all samples. Furthermore, RNA dot-blot analysis with digoxigenin-labeled RNA probe and immunohistochemistry with JSB-1 and C-219 antibodies for P-glycoprotein were employed in 34 and 37 samples in soft tissue sarcomas, respectively. We compared these three detection techniques. Of the 39 specimens, 18 (46%) showed MDR1 PCR products. Liposarcomas (six of 11), malignant fibrous histiocytomas (six of nine), leiomyosarcomas (four of six), fibrosarcomas (two of three) revealed high or intermediate MDR1 expression at high frequency. No MDR1 expression was detectable in malignant schwannomas, synovial sarcomas, or epithelioid sarcomas. Of seven benign soft tissue tumors, one ganglioneuroma and one lipomatosis showed low levels of MDR1 expression. By RNA dot-blot analysis, MDR1 transcripts were detectable in 12 of 34 specimens (35%). Four samples were negative by dot blot despite positivity with RT-PCR. Concordance between MDR1 expression by RNA level with RT-PCR and dot blot and at the protein level with immunohistochemistry using C-219 was found in 16 (47%) of the 34 comparable specimens. Eight samples showed positive immunoreactivity for C-219 despite negative results in RT-PCR and dot-blot analysis. The intrinsic MDR1 expression in soft tissue sarcoma seemed to depend on certain tumor types, such as liposarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and fibro-sarcoma. For the evaluation of MDR1 expression, RT-PCR is useful because of its relative simplicity and sensitivity. However, the clinical significance of such low levels of MDR1 expression detected only by RT-PCR must be discussed within systematically treated patient groups. (C) Lippincott-Raven Publishers.