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卵巢癌免疫表型作为临床结局预测指标:在初次手术及二次探查术中的评估

Immunophenotype of ovarian cancer as predictor of clinical outcome: evaluation at primary surgery and second-look procedure.

作者信息

Goff B A, Ries J A, Els L P, Coltrera M D, Gown A M

机构信息

Department of Obstetrics and Gynecology, University of Washington Medical Center, Seattle, Washington, 98195, USA.

出版信息

Gynecol Oncol. 1998 Sep;70(3):378-85. doi: 10.1006/gyno.1998.5094.

Abstract

OBJECTIVE

This study was undertaken to evaluate whether immunophenotyping of advanced epithelial ovarian cancer could predict response to initial chemotherapy and whether tumor immunophenotype changed after chemotherapy.

STUDY DESIGN

Fifty-four patients with stage III and IV ovarian cancer, treated at the University of Washington Medical Center, had pathology specimens evaluated. A subset of 23 patients also had specimens from a secondary surgery evaluated. Using immunocytochemistry, tumors were immunostained for overexpression of c-erb-B-2, epidermal growth factor receptor (EGFR), p53, and expression of the Ki67-defined antigen (a marker of cellular proliferation), tumor necrosis factor alpha (TNFalpha), estrogen receptor (ER), progesterone receptor (PR), and P-glycoprotein (P170, a marker of multidrug resistance). Twenty-four patients had a good response to chemotherapy (defined as a negative, or microscopically positive second look), and 30 had a poor response (defined as grossly positive second look or progressive disease).

RESULTS

Comparison of tumor markers from the initial and the secondary surgeries revealed that the only significant change was in the Ki67-defined cell proliferation rate, which showed a marked reduction in those with a good response to chemotherapy (P = 0.002). Comparison of tumor markers at initial surgery between good and poor responders revealed a correlation with p53 expression. Good responders were less likely to have p53 overexpression compared to poor responders, and this result approached significance (P = 0.058). Comparison of tumor markers at secondary surgery revealed a significant reduction in Ki67-defined cell proliferation rate in good responders compared to poor responders (P = 0.01). No significant differences were found between good and poor responders for the other tumor markers evaluated.

CONCLUSIONS

The only tumor markers to predict for response to chemotherapy were p53 at initial surgery (P = 0.058) and Ki67 indices at secondary surgery (P = 0.001). Expression of steroid hormone receptors, TNFalpha, and P-glycoprotein and overexpression of c-erb-B-2 or EGFR are not associated with chemoresistance.

摘要

目的

本研究旨在评估晚期上皮性卵巢癌的免疫表型是否能够预测对初始化疗的反应,以及化疗后肿瘤免疫表型是否发生变化。

研究设计

在华盛顿大学医学中心接受治疗的54例III期和IV期卵巢癌患者的病理标本得到评估。23例患者的子集还对二次手术的标本进行了评估。使用免疫细胞化学方法,对肿瘤进行免疫染色,以检测c-erb-B-2、表皮生长因子受体(EGFR)、p53的过表达,以及Ki67定义抗原(细胞增殖标志物)、肿瘤坏死因子α(TNFα)、雌激素受体(ER)、孕激素受体(PR)和P-糖蛋白(P170,多药耐药标志物)的表达。24例患者对化疗反应良好(定义为二次探查阴性或显微镜下阳性),30例反应较差(定义为二次探查肉眼阳性或疾病进展)。

结果

初次手术和二次手术肿瘤标志物的比较显示,唯一显著的变化是Ki67定义的细胞增殖率,化疗反应良好者的该指标显著降低(P = 0.002)。初次手术时反应良好者与反应较差者肿瘤标志物的比较显示与p53表达相关。与反应较差者相比,反应良好者p53过表达的可能性较小,但该结果接近显著性(P = 0.058)。二次手术时肿瘤标志物的比较显示,反应良好者与反应较差者相比,Ki67定义的细胞增殖率显著降低(P = 0.01)。对于所评估的其他肿瘤标志物,反应良好者与反应较差者之间未发现显著差异。

结论

预测化疗反应的唯一肿瘤标志物是初次手术时的p53(P = 0.058)和二次手术时的Ki67指数(P = 0.001)。甾体激素受体、TNFα和P-糖蛋白的表达以及c-erb-B-2或EGFR的过表达与化疗耐药无关。

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