HER-2/neu overexpression in uterine papillary serous cancers and its possible therapeutic implications
HER-2/neu overexpression in uterine papillary serous cancers and its possible therapeutic implications
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DOI：
10.1111/j.1525-1438.2006.00664.x
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发表时间：
2006-09-01
影响因子：
4.8
通讯作者：
Hershman, D.
中科院分区：
文献类型：
--
作者：
Villella, J. A.;Cohen, S.;Hershman, D.
子宫乳头状浆液性癌（UPSC）是子宫内膜癌的一种高度侵袭性变体，其特征与高级别卵巢癌相似。患者往往年老、瘦弱、诊断时肿瘤级别较高且患有广泛的宫外病变。 HER-2 细胞癌基因编码的跨膜受体在多种类型的人类癌症中被扩增，并提供了一个有吸引力的治疗靶点。免疫组织化学显示，HER-2/neu 是由 c-erbB2 基因编码的跨膜受体，在 < 25% 的卵巢癌、20-30% 的乳腺癌和 < 10% 的子宫内膜癌中过表达。这种跨膜蛋白的过度表达具有与预后和治疗相关的意义。赫赛汀是一种针对 HER-2/neu 蛋白胞外结构域的人源化鼠单克隆抗体，用于治疗过度表达 HER-2/neu 的乳腺癌。我们回顾了 1999 年至 2001 年间诊断为 UPSC 的所有患者。确定了 26 名患者，其中 19 名患者有可供评估的标本。我们对 19 个石蜡包埋的 UPSC 肿瘤块进行了免疫组织化学分析（Herceptest，Dako，Carpinteria，CA），寻找 HER-2/neu 过度表达。 19 个中的 5 个 (26%) 出现 HER-2/neu 受体蛋白重度染色 (3+)。这五名患者中有四人在诊断时已处于晚期疾病。其中两名患者随后接受了赫赛汀治疗；根据 CT 扫描和 CA-125 结果，一名患者完全缓解，一名患者病情稳定。靶向 HER-2/neu 可能对特定的 UPSC 患者有益。我们正在继续通过荧光原位杂交 (FISH) 评估样品的 HER-2/neu 过度表达。
Uterine papillary serous carcinoma (UPSC) is a highly aggressive variant of endometrial cancer with features similar to high-grade ovarian cancer. Patients tend to be elderly, thin, have a high grade tumor with extensive extrauterine disease at the time of diagnosis. The transmembrane receptor encoded by the HER-2 cellular oncogene is amplified in several types of human carcinomas and provides an attractive therapeutic target. HER-2/neu, the transmembrane receptor encoded by the c-erbB2 gene, is overexpressed by immunohistochemistry in < 25% of ovarian cancers and 20-30% of breast cancers, and < 10% of endometrial cancer. There are prognostic and therapeutic implications associated with the overexpression of this transmembrane protein. Herceptin, a humanized murine monoclonal antibody directed against the extracellular domain of the HER-2/neu protein, is being used to treat breast cancer that overexpresses HER-2/neu. We reviewed all patients diagnosed with UPSC between 1999-2001. Twenty-six patients were identified, and 19 patients had specimens available for evaluation. We performed immunohistochemical analysis (Herceptest, Dako, Carpinteria, CA) on 19 paraffin embedded blocks of UPSC tumors looking for HER-2/neu over expression. Five out of 19 (26%) stained heavily (3+) for HER-2/neu receptor protein. Four of these five patients had advanced disease at diagnosis. Two of these patients were subsequently treated with Herceptin; one with complete response and one with stable disease based on CT scan and CA-125 findings. Targeting HER-2/neu may be beneficial for a select group of patients with UPSC. We are continuing to evaluate samples for HER-2/neu over expression by fluorescence in situ hybridization (FISH).