Oda Y, Schneider-Stock R, Ryś J, Gruchała A, Niezabitowski A, Roessner A
Institute of Pathology, Otto-von-Guericke University, Magdeburg, Germany.
Diagn Mol Pathol. 1996 Jun;5(2):98-106. doi: 10.1097/00019606-199606000-00004.
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 fibrosarcoma. 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.
据报道，多药耐药基因MDR1的表达是某些癌症化疗反应和生存的重要决定因素。我们比较了三种测定软组织肉瘤中固有MDR1表达的方法。我们研究了33例软组织肉瘤的39个样本中的MDR1基因表达，其中包括11例脂肪肉瘤、9例恶性纤维组织细胞瘤、6例平滑肌肉瘤、4例恶性神经鞘瘤、3例纤维肉瘤、3例滑膜肉瘤和3例上皮样肉瘤，以及7例成年患者的良性软组织肿瘤。为了检测MDR1 mRNA，对所有样本进行了逆转录聚合酶链反应（RT-PCR）。此外，分别对34例软组织肉瘤样本采用地高辛标记RNA探针进行RNA斑点杂交分析，对37例软组织肉瘤样本采用JSB-1和C-219抗体进行P-糖蛋白免疫组织化学检测。我们比较了这三种检测技术。在39个标本中，18个（46%）显示出MDR1 PCR产物。脂肪肉瘤（11例中的6例）、恶性纤维组织细胞瘤（9例中的6例）、平滑肌肉瘤（6例中的4例）、纤维肉瘤（3例中的2例）高频显示高或中度MDR1表达。在恶性神经鞘瘤、滑膜肉瘤或上皮样肉瘤中未检测到MDR1表达。在7例良性软组织肿瘤中，1例神经节神经瘤和1例脂肪瘤显示低水平的MDR1表达。通过RNA斑点杂交分析，在34个标本中的12个（35%）检测到MDR1转录本。尽管RT-PCR呈阳性，但有4个样本斑点杂交呈阴性。在34个可比较标本中的16个（47%）中，发现RT-PCR和斑点杂交检测的RNA水平的MDR1表达与使用C-219免疫组织化学检测的蛋白质水平的MDR1表达一致。尽管RT-PCR和斑点杂交分析结果为阴性，但有8个样本C-219免疫反应呈阳性。软组织肉瘤中的固有MDR1表达似乎取决于某些肿瘤类型，如脂肪肉瘤、恶性纤维组织细胞瘤、平滑肌肉瘤和纤维肉瘤。对于MDR1表达的评估，RT-PCR因其相对简单和灵敏而有用。然而，仅通过RT-PCR检测到的这种低水平MDR1表达的临床意义必须在系统治疗的患者组中进行讨论。
