Absence of p53 overexpression and favorable response to cisplatin-based neoadjuvant chemotherapy in urothelial carcinomas
Absence of p53 overexpression and favorable response to cisplatin-based neoadjuvant chemotherapy in urothelial carcinomas
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DOI：
10.1111/j.1349-7006.1998.tb00551.x
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发表时间：
1998-02-01
期刊：
影响因子：
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通讯作者：
Yoshida, O
中科院分区：
文献类型：
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作者：
Kakehi, Y;Özdemir, E;Yoshida, O
肿瘤抑制因子 p53 缺失或失活的癌细胞对顺铂和阿霉素等 DNA 损伤剂是否具有耐药性或敏感度一直存在争议。 mdm2 癌蛋白（p53 的负调节因子）的过度表达被认为是 p53 功能障碍的替代方案。对在基于顺铂的化疗之前从 60 名患者获得的存档尿路上皮癌标本进行了免疫组织化学研究，以了解 p53 和 mdm2 的过度表达。 32 名患者（第一组）在新辅助治疗中接受化疗，而 28 名患者（第二组）因远处转移或无法手术的局部肿瘤接受化疗。在第一组中，反应性与p53的染色状态（P=0.0225）以及p53和mdm2的组合（P=0.0497）相关。 p53 阴性染色以及 p53 和 mdm2 阴性染色分别可预测 18 个肿瘤中的 16 个 (88.9%) 和 13 个肿瘤中的 12 个 (92.3%) 对化疗的良好反应。另一方面，p53 阳性和 p53 和/或 mdm2 阳性染色只能预测 14 个肿瘤中的 7 个 (50.0%) 和 19 个肿瘤中的 8 个肿瘤的不良反应(42.1%) 个肿瘤，p53 阴性组的疾病特异性生存率显着优于 p53 阳性组 (P=0.0086)，当考虑到 mdm2 的过表达时，生存率差异并没有变得更加显着 (P=0.0456)。相反，在 II 组中，化疗反应或生存率与 p53 或 p53/mdm2 染色状态没有相关性。 p53过度表达阴性的尿路上皮癌患者将受益于新辅助化疗，然而，从临床角度来看，单独的p53状态或p53和mdm2状态的组合不足以识别那些不会从治疗中受益的患者。
It has been controversial whether cancer cells harboring loss or inactivation of the tumor suppressor p53 are resistant or sensitive to DNA-damaging agents including cisplatin and doxorubicin. Overexpression of mdm2 oncoprotein, a negative regulator of p53, is assumed to be an alternative to p53 dysfunction. Archival urothelial carcinoma specimens obtained from 60 patients prior to cisplatin-based chemotherapy were immunohistochemically studied for overexpression of p53 and mdm2. Thirty-two patients (group I) were treated with chemotherapy in the neoadjuvant setting, while 28 patients (group II) underwent chemotherapy for distant metastases or inoperable locoregional tumors. In group I, the responsiveness was correlated with staining status of p53 (P=0.0225) and the combination of p53 and mdm2 (P=0.0497). Negative staining of p53 and negative for both p53 and mdm2 could have predicted favorable response to chemotherapy in 16 of 18 (88.9%) and in 12 of 13 (92.3%) tumors, respectively, On the other hand, p53-positive and p53 and/or mdm2-positive staining could have predicted poor response only in 7 of 14 (50.0%) and 8 of 19 (42.1%) tumors, respectively, Disease-specific survival of the p53-negative group was significantly superior to that of the p53-positive group (P=0.0086), Difference in survival did not become more significant when overexpression of mdm2 was taken into consideration (P=0.0456), In contrast, in group II, there was no correlation of responsiveness to chemotherapy or survival with p53- or p53/mdm2-staining status. The patients with urothelial carcinomas negative for overexpression of p53 will benefit from neoadjuvant chemotherapy, From clinical viewpoint, however, p53 status alone or the combination of p53 and mdm2 status is not enough to identify those patients who will not benefit from the treatment.