选择HER2/NEU阴性肿瘤细胞作为子宫浆液性癌对曲妥珠单抗耐药的一种机制。
Selection of HER2/NEU negative tumor cells as a mechanism of resistance to trastuzumab in uterine serous carcinoma.
作者信息
Pelligra Silvia, Buza Natalia, Hui Pei, Bellone Stefania, Zeybek Burak, Ratner Elena, Schwartz Peter E, Scambia Giovanni, Santin Alessandro D
机构信息
Department of Obstetrics, Gynecology, and Reproductive Sciences, New Haven, CT 06520, USA.
Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.
出版信息
Gynecol Oncol Rep. 2020 Feb 25;32:100554. doi: 10.1016/j.gore.2020.100554. eCollection 2020 May.
BACKGROUND
Uterine serous carcinoma (USC) is an aggressive variant of endometrial cancer overexpressing HER2/neu in about 30% of cases. Trastuzumab, a humanized monoclonal antibody targeting Her2/Neu, in combination with carboplatin/paclitaxel, is considered the preferred regimen for the treatment of advanced or recurrent HER2/Neu+ USC per NCCN guidelines.
CASE
We describe two USC patients with overexpression of HER2/neu at 2+/3+ level by immunohistochemistry and c-erbB2 gene amplification by fluorescence in situ hybridization (FISH) assay that, after an initial clinical response to trastuzumab, developed resistance/progression. Post-treatment biopsy (collected at the time of clinical progression on trastuzumab) demonstrated loss of HER2/neu overexpression in the recurrent/progressing tumor cells in both patients.
CONCLUSION
Selection of HER2/NEU negative tumor cells may represent a major mechanism of resistance to trastuzumab in USC patients.
背景
子宫浆液性癌（USC）是子宫内膜癌的一种侵袭性变体，约30%的病例中HER2/neu过表达。曲妥珠单抗是一种靶向Her2/Neu的人源化单克隆抗体，根据美国国立综合癌症网络（NCCN）指南，与卡铂/紫杉醇联合使用被认为是治疗晚期或复发性HER2/Neu+ USC的首选方案。
病例
我们描述了两名USC患者，通过免疫组织化学检测HER2/neu在2+/3+水平过表达，通过荧光原位杂交（FISH）检测c-erbB2基因扩增，这两名患者在对曲妥珠单抗产生初始临床反应后出现耐药/进展。治疗后活检（在曲妥珠单抗临床进展时采集）显示，两名患者复发/进展的肿瘤细胞中HER2/neu过表达均消失。
结论
选择HER2/NEU阴性肿瘤细胞可能是USC患者对曲妥珠单抗耐药的主要机制。
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