PROGNOSTIC-SIGNIFICANCE OF HER-2/NEU EXPRESSION IN ADVANCED EPITHELIAL OVARIAN-CANCER - A MULTIVARIATE-ANALYSIS

PROGNOSTIC-SIGNIFICANCE OF HER-2/NEU EXPRESSION IN ADVANCED EPITHELIAL OVARIAN-CANCER - A MULTIVARIATE-ANALYSIS
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DOI:
10.1016/s0002-9378(12)90907-2
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发表时间:
1993-01-01
影响因子:
9.8
通讯作者:
LLOYD, KO
LLOYD, KO
中科院分区:
医学1区
文献类型:
--
作者:
RUBIN, SC;FINSTAD, CL;LLOYD, KO

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目的:正如先前的研究所表明的那样,我们检验了原癌基因 HER-2/neu 的表达水平在晚期卵巢癌中具有预后意义的假设。 研究设计:我们使用单克隆抗体 9G6 和间接免疫过氧化物酶技术,通过免疫组织化学测定了 105 例 III 期或 IV 期上皮性卵巢癌患者的冷冻肿瘤标本中 HER-2/neu 的表达。所有患者均在纪念斯隆-凯特琳癌症中心接受治疗,没有患者失访。存活患者的中位随访时间为 34 个月。 HER-2/neu 表达评分为阴性、弱、1+、2+ 或 3+。正常卵巢上皮的染色模式评分为阴性至1+。进行多变量分析以评估 HER-2/neu 表达的预后意义。 结果:105 名患者中的 25 名 (24%) 表现出强烈的膜染色 (3+);其他肿瘤标本显示较弱的膜染色或无免疫反应性。 HER-2/neu 表达与多种临床因素(包括分期、分级、细胞类型和残留肿瘤)均无相关性。染色强度水平与正常卵巢上皮相似的患者和表达增加的患者(3+)之间没有发现显着的生存差异。两组的中位生存时间分别为 36 个月和 27 个月(95% 置信区间为 29 至 45 个月和 18 至 39 个月)。对可能的预后因素的多变量分析表明,HER-2/neu 过度表达导致化疗后手术重新评估未达到阴性的亚组患者的生存率略有恶化 (p = 0.09)。 结论:HER-2/neu 表达似乎不是晚期上皮性卵巢癌患者的重要预后因素。
OBJECTIVE: We tested the hypothesis that there is prognostic significance to the level of expression of the protooncogene HER-2/neu in advanced ovarian cancer, as prior studies have suggested.STUDY DESIGN: We determined expression of HER-2/neu by immunohistochemistry, with monoclonal antibody 9G6 and the indirect immunoperoxidase technique, on frozen tumor specimens from 105 patients with stage III or IV epithelial ovarian cancer. All patients were treated at Memorial Sloan-Kettering Cancer Center, and no patient was lost to follow-up. Median follow-up among surviving patients is 34 months. HER-2/neu expression was scored as negative, weak, 1+, 2+, or 3+. The staining pattern of normal ovarian epithelium was scored negative to 1+. Multivariate analysis was performed to evaluate the prognostic significance of HER-2/neu expression.RESULTS: Twenty-five of the 105 patients (24%) showed strong membrane staining (3+); the other tumor specimens showed weaker membrane staining or no immunoreactivity. There was no correlation of HER-2/neu expression with any of a variety of clinical factors, including stage, grade, cell type, and residual tumor. No significant survival difference was found between patients with levels of staining intensity similar to those of normal ovarian epithelium and those with increased expression (3+). Median survival times were 36 and 27 months, respectively, for the two groups (95% confidence intervals 29 to 45 and 18 to 39 months). Multivariate analysis of possible prognostic factors showed that HER-2/neu overexpression conferred a marginal worsening of survival (p = 0.09) for the subgroup of patients in whom a negative surgical reassessment was not achieved after chemotherapy.CONCLUSION: HER-2/neu expression does not appear to be an important prognostic factor in patients with advanced epithelial ovarian cancer.