Rubin S C, Finstad C L, Wong G Y, Almadrones L, Plante M, Lloyd K O
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Am J Obstet Gynecol. 1993 Jan;168(1 Pt 1):162-9. doi: 10.1016/s0002-9378(12)90907-2.
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.
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.
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.
HER-2/neu expression does not appear to be an important prognostic factor in patients with advanced epithelial ovarian cancer.
正如先前研究所提示的，我们检验了原癌基因HER-2/neu的表达水平对晚期卵巢癌具有预后意义这一假说。
我们采用单克隆抗体9G6及间接免疫过氧化物酶技术，通过免疫组化法测定了105例Ⅲ期或Ⅳ期上皮性卵巢癌患者冷冻肿瘤标本中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，且无一例患者失访。存活患者的中位随访时间为34个月。HER-2/neu表达分为阴性、弱阳性（1+）、阳性（2+）或强阳性（3+）。正常卵巢上皮的染色模式评分为阴性至1+。进行多因素分析以评估HER-2/neu表达的预后意义。
105例患者中有25例（24%）表现为强膜染色（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均无相关性，包括分期、分级、细胞类型及残留肿瘤。染色强度与正常卵巢上皮相似的患者和表达增加（3+）的患者之间未发现显著的生存差异。两组的中位生存时间分别为36个月和27个月（95%可信区间分别为29至45个月和18至39个月）。对可能的预后因素进行多因素分析显示，对于化疗后手术再评估为阴性未实现的患者亚组，HER-2/neu过表达使生存略有恶化（p = 0.09）。
HER-2/neu表达似乎并非晚期上皮性卵巢癌患者的重要预后因素。
