p53 gene status and response to platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma
p53 gene status and response to platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma
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DOI：
10.1200/jco.2000.18.23.3936
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发表时间：
2000-12-01
影响因子：
45.3
通讯作者：
Zunino, F
中科院分区：
文献类型：
--
作者：
Lavarino, C;Pilotti, S;Zunino, F
目的：p53 基因在细胞对 DNA 损伤的反应中发挥着关键作用，并且与卵巢癌患者对铂化合物的反应有关。由于紫杉烷类药物可诱导不依赖于 p53 的细胞凋亡，因此我们评估了 p53 基因状态与接受紫杉醇和含铂化疗的卵巢癌患者的反应的相关性。 患者和方法：48 名既往未经治疗的晚期疾病患者接受了标准紫杉醇/铂类化疗。在初次手术时、治疗前收集的肿瘤标本中，通过单链构象多态性、序列分析和免疫组织化学分析检查p53基因状态和表达。对 30 名患者的可用采样器进行了微卫星不稳定性分析。结果：48 名患者中有 34 名 (71%) 出现 CT 临床反应。 48 名患者中有 13 名（27%）病理完全缓解。在 48 个肿瘤中的 29 个 (60%) 中检测到 p53 突变。在 p53 突变肿瘤患者中，25 名患者 (86%) 对化疗有反应。 19 名野生型 p53 肿瘤患者中只有 9 名（47%）对相同的治疗有反应。突变型 p53 肿瘤患者的总体缓解率和完全缓解率显着高于野生型 p53 肿瘤患者 (P = .008)。大多数与完全缓解无关的测试肿瘤（12 个肿瘤中的 10 个）也具有微卫星不稳定性的特征。无微卫星不稳定的肿瘤患者的完全缓解率较高（七名患者中的五名）。 结论：与紫杉醇联合标准铂剂量治疗野生型 p53 卵巢肿瘤的有限疗效相比，突变型 p53 卵巢肿瘤患者对基于紫杉醇的化疗反应更灵敏。对含有紫杉醇的化疗的反应模式与高剂量顺铂治疗的反应模式不同。确定 p53 突变状态可有助于预测对卵巢癌有效药物的治疗反应。 (C) 2000 年美国临床肿瘤学会。
Purpose: The p53 gene plays a critical role in cellular response to DNA damage and has been implicated in the response to platinum compounds in ovarian carcinoma patients. Because taxanes could induce p53-independent apoptosis, we assessed the relevance of p53 gene status to response in ovarian carcinoma patients receiving paclitaxel and platinum-containing chemotherapy.Patients and Methods: Forty-eight previously untreated patients with advanced disease received standard paclitaxel/platinum-based chemotherapy. In tumor specimens collected at the time of initial surgery, before therapy, p53 gene status and expression were examined by single-strand conformation polymorphism, sequence analysis, and immunohistochemical analysis. Microsatellite instability analysis was performed on available sampler from 30 patients.Results: Thirty-four (71%) of the 48 patients had ct clinical response. Pathologic complete remission was documented in 13 (27%) of 48 patients. p53 mutations were detected in 29 (60%) of 48 tumors. Among the patients with mutant p53 tumors, 25 patients (86%) responded to chemotherapy. Only nine (47%) of 19 patients with wild-type p53 tumors responded to the same treatment. The overall response rate and the complete remission rate were significantly higher among patients with mutant p53 tumors than among patients with wild-type p53 tumors (P = .008). Most of the tested tumors not associated with complete remission (10 of 12 tumors) were also characterized by microsatellite instability. The complete remission rate was higher among patients with tumors without microsatellite instability (five of seven patients).Conclusion: In contrast to the limited efficacy of treatment with paclitaxel in combination with standard platinum doses against wild-type p53 ovarian tumors, patients with mutant p53 ovarian tumors were more responsive to paclitaxel-based chemotherapy. The pattern of response to chemotherapy containing paclitaxel is different from that associated with high-dose cisplatin therapy. Determining p53 mutational status can be useful in predicting therapeutic response to drugs effective in ovarian carcinoma. (C) 2000 by American Society of Clinical Oncology.