Nakanishi H, Myoui A, Ochi T, Aozasa K
Department of Pathology, Osaka University Medical School, Japan.
J Cancer Res Clin Oncol. 1997;123(6):352-6. doi: 10.1007/BF01438312.
Multidrug resistance (MDR) is an important problem in chemotherapy for neoplastic disease. In humans. MDR is mainly mediated by P-glycoprotein (P-gp) a product of the MDRI gene, which acts as a transmembrane protein pump and eliminates chemotherapeutic agents from the cells. Expression of P-gp was immunohistochemically studied by using two monoclonal antibodies, JSB-1 and C-219, on paraffin-embedded sections from 55 patients with soft-tissue sarcoma. The histological diagnosis of tumors was malignant fibrous histiocytoma in 24 cases, liposarcoma in 9, synovial sarcoma in 7, malignant neurogenic tumors in 6, leiomyosarcoma in 5, others in 4. The histological grade was determined on the basis of criteria previously proposed by us. Out of 55 cases, 34 (62%) were positive for P-gp expression. There was a significant difference in P-gp expression between high-grade (90%) and intermediate and low-grade tumors (46%) (P < 0.005). Tumors expressing P-gp had a less favorable prognosis than P-gp-negative tumors in the high- and intermediate-grade tumors. The current study demonstrated that the estimation of P-gp expression could be used to select appropriate therapeutic modalities.
多药耐药性(MDR)是肿瘤疾病化疗中的一个重要问题。在人类中,MDR主要由MDR1基因的产物P-糖蛋白(P-gp)介导,P-gp作为一种跨膜蛋白泵,可将化疗药物从细胞中清除。使用两种单克隆抗体JSB-1和C-219,对55例软组织肉瘤患者石蜡包埋切片进行免疫组织化学研究,以检测P-gp的表达。肿瘤的组织学诊断为恶性纤维组织细胞瘤24例,脂肪肉瘤9例,滑膜肉瘤7例,恶性神经源性肿瘤6例,平滑肌肉瘤5例,其他4例。组织学分级根据我们之前提出的标准确定。55例病例中,34例(62%)P-gp表达呈阳性。高级别肿瘤(90%)与中低级别肿瘤(46%)的P-gp表达存在显著差异(P<0.005)。在高级别和中级别肿瘤中,表达P-gp的肿瘤预后比P-gp阴性肿瘤差。当前研究表明,P-gp表达的评估可用于选择合适的治疗方式。