Röhlke P, Milde-Langosch K, Weyland C, Pichlmeier U, Jonat W, Löning T
Clinic of Gynecology and Obstetrics, University Hospital of Hamburg, Germany.
J Cancer Res Clin Oncol. 1997;123(9):496-501. doi: 10.1007/BF01192204.
p53 mutation and p53 protein overexpression are common findings in ovarian carcinomas. In order to evaluate the prognostic significance of the p53 status and its role in metastasis, we examined 104 ovarian carcinomas, among them 83 cases with follow-up data, and 40 pairs of primary tumors and metastases, by p53 immunohistochemistry and temperature-gradient gel electrophoresis. Comparison of primary tumors and their metastases revealed identical results in 88%-90% of the cases, indicating that, in most cases, mutant p53 occurs prior to metastatic spread and remains clonally conserved. With respect to all tumors, moderate/high p53 expression was significantly more prevalent in serous-papillary types, carcinomas with high grade, and high Ki67 scores, but was not associated with age, stage, or hormone receptor status. Kaplan-Meier analysis of 83 cases, followed-up for 9-96 months, demonstrated that moderate/high p53 overexpression in the group of 66 stage T3/M1 tumors was associated significantly (P = 0.0028 and P = 0.0105) with shorter overall and recurrence-free survival. Multivariate analysis revealed that advanced clinical stage and p53 positivity were the only independent predictive variables. No significance was seen in regard to second-look results and outcome of 50 patients receiving platinum-based chemotherapy. These observations show that p52 immunohistochemistry is an independent prognostic indicator at the given cut-off level, but does not reliably predict chemotherapy response.
p53突变和p53蛋白过表达是卵巢癌中的常见现象。为了评估p53状态的预后意义及其在转移中的作用，我们通过p53免疫组织化学和温度梯度凝胶电泳检查了104例卵巢癌，其中83例有随访数据，以及40对原发性肿瘤和转移灶。原发性肿瘤与其转移灶的比较显示，88%-90%的病例结果相同，这表明在大多数情况下，突变型p53在转移扩散之前就已出现，并且保持克隆保守性。就所有肿瘤而言，中度/高度p53表达在浆液性乳头状类型、高级别癌和高Ki67评分的癌中明显更为普遍，但与年龄、分期或激素受体状态无关。对83例随访9-96个月的病例进行的Kaplan-Meier分析表明，66例T3/M1期肿瘤组中的中度/高度p53过表达与总体生存期和无复发生存期显著缩短相关（P = 0.0028和P = 0.0105）。多变量分析显示，晚期临床分期和p53阳性是仅有的独立预测变量。对于50例接受铂类化疗患者的二次探查结果和预后，未发现显著意义。这些观察结果表明，在给定的临界水平下，p53免疫组织化学是一个独立的预后指标，但不能可靠地预测化疗反应。
