p53 status correlates with histopathological response in patients with soft tissue sarcomas treated using isolated limb perfusion with TNF-α and melphalan
p53 status correlates with histopathological response in patients with soft tissue sarcomas treated using isolated limb perfusion with TNF-α and melphalan
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DOI：
10.1093/annonc/mdm559
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发表时间：
2008-04-01
影响因子：
50.5
通讯作者：
Chouaib, S.
中科院分区：
文献类型：
--
作者：
Muret, J.;Yacoub, M.;Chouaib, S.
背景资料：重组肿瘤坏死因子-α（TNF-α）与美法仑的组合在临床上通过隔离肢体灌注（ILP）用于肢体局部晚期软组织肉瘤。在临床前研究中，野生型p53基因参与调节TNF-α的细胞毒性作用，并且p53功能的丧失有助于肿瘤细胞对TNF-α的抗性。P53状态和对TNF-α和美法仑的反应在接受ILP的患者之间的关系是unknown.Patients和方法：我们研究了110例不可切除的四肢肉瘤ILP治疗。使用DO 7 mAb和PAb 1620 mAb进行免疫组织化学，DO 7 mAb与野生型和突变型p53蛋白的N-末端区域的抗原决定簇反应，PAb 1620 mAb与野生型p53蛋白天然构象的1620表位特征反应.结果：P53 DO 7高表达28例，PAb 1620阴性20例。组织学反应较差的肿瘤ILP与TNF-α andmelphalan表现出显着较高水平的p53突变蛋白。结论：我们的研究结果可能是一个线索的作用，p53蛋白的状态，TNF-α和melphalan反应在临床使用。
Background: Recombinant tumor necrosis factor-alpha ( TNF-alpha) combined to melphalan is clinically administered through isolated limb perfusion ( ILP) for regionally advanced soft tissue sarcomas of the limbs. In preclinical studies, wild- type p53 gene is involved in the regulation of cytotoxic action of TNF-alpha and loss of p53 function contributes to the resistance of tumour cells to TNF-alpha. The relationship between p53 status and response to TNF-alpha and melphalan in patients undergoing ILP is unknown.Patients and methods: We studied 110 cases of unresectable limbs sarcomas treated by ILP. Immunohistochemistry was carried out using DO7mAb, which reacts with an antigenic determinant from the N- terminal region of both the wild- type and mutant forms of the p53 protein, and PAb1620mAb, which reacts with the 1620 epitope characteristic of the wild- type native conformation of the p53 protein. The immunohistochemistry data were then correlated with various clinical parameters.Results: P53DO7 was found expressed at high levels in 28 patients, whereas PAb1620 was negative in 20. The tumours with poor histological response to ILPwith TNF-alpha andmelphalan showed significantly higher levels of p53- mutated protein.Conclusions: Our results might be a clue to a role of p53 protein status in TNF-alpha and melphalan response in clinical use.