Radig K, Häckel C, Herting J, Oda Y, Mittler U, Neumann W, Roessner A
Department of Pathology, Otto-von-Guericke-University, Magdeburg, Germany.
Gen Diagn Pathol. 1997 Feb;142(3-4):139-45.
The development of chemoresistance is one of the major clinical problems in the therapy of malignant bone tumors in childhood. The expression of membrane-bound P-glycoprotein turned out to be an essential factor in the evidence of resistant tumor cells. To investigate the significance of multidrug resistance in the prognosis of highly malignant osteosarcomas, the immunohistologic expression of P-glycoprotein was investigated in the tumor tissue of 52 patients under special consideration of the histologic subtype. The data were compared with the histologic regression grade in the resection specimen and correlated with clinical data. Formalin-fixed, paraffin-embedded tissue and, additionally, fresh frozen material taken from the primary biopsy were stained using monoclonal antibody JSB1. 29 (55%) of the tumors investigated were P-glycoprotein positive. Considering the response to chemotherapy, no conclusion could be drawn regarding P-glycoprotein expression, regression grade in the resection specimens, and the clinical follow-up. P-glycoprotein was detected in only 52% of the non-responders. A positive reaction was also evidenced in 59% of the patients with high chemosensitivity. A comparison of the histologic subtypes yielded a significant result in the chondroblastic osteosarcomas. 11 of 12 cases showed a strong expression of P-glycoprotein. Most of the cases were non-responders, and using Kaplan-Meier live tables, an unfavorable clinical outcome could be demonstrated. Possibly, chondroblastic tumors have a special position among osteosarcomas because of their differentiation.
化疗耐药的发展是儿童恶性骨肿瘤治疗中的主要临床问题之一。膜结合型P-糖蛋白的表达被证明是耐药肿瘤细胞证据中的一个重要因素。为了研究多药耐药在高度恶性骨肉瘤预后中的意义，在特别考虑组织学亚型的情况下，对52例患者的肿瘤组织中P-糖蛋白的免疫组织化学表达进行了研究。将数据与切除标本中的组织学消退分级进行比较，并与临床数据相关联。使用单克隆抗体JSB1对福尔马林固定、石蜡包埋的组织以及另外从初次活检获取的新鲜冷冻材料进行染色。所研究的肿瘤中有29例（55%）P-糖蛋白呈阳性。考虑到对化疗的反应，关于P-糖蛋白表达、切除标本中的消退分级以及临床随访无法得出结论。仅在52%的无反应者中检测到P-糖蛋白。在59%化疗敏感性高的患者中也证实有阳性反应。组织学亚型的比较在软骨母细胞型骨肉瘤中得出了显著结果。12例中有11例显示P-糖蛋白强表达。大多数病例为无反应者，使用Kaplan-Meier生存表，可以证明临床结局不佳。可能由于其分化情况，软骨母细胞性肿瘤在骨肉瘤中具有特殊地位。
