The role of HER2 as a therapeutic biomarker in gynaecological malignancy: potential for use beyond uterine serous carcinoma

被引:15
作者
Talia, Karen L. [1 ,2 ,5 ]
Banet, Natalie [3 ]
Buza, Natalia [4 ]
机构
[1] Royal Womens Hosp, Royal Childrens Hosp, Melbourne, Vic, Australia
[2] Australian Ctr Prevent Cerv Canc, Melbourne, Vic, Australia
[3] Dept Pathol, Cleveland Clin, Cleveland, OH USA
[4] Yale Univ, Dept Pathol, Sch Med, New Haven, CT USA
[5] Royal Womens Hosp, Dept Anat Pathol, Level 5,20 Flemington Rd, Parkville, Vic 3052, Australia
关键词
HER2; testing; ERBB2; biomarker; immunohistochemistry; fluorescent in situ hybridisation; uterine serous carcinoma; EXTRAMAMMARY PAGETS-DISEASE; HUMAN-BREAST-CANCER; PHASE-II TRIAL; HER-2/NEU OVEREXPRESSION; ENDOMETRIAL CANCER; GENE AMPLIFICATION; PROTEIN OVEREXPRESSION; ADJUVANT CHEMOTHERAPY; AMERICAN-PATHOLOGISTS; PAPILLARY CARCINOMA;
D O I
10.1016/j.pathol.2022.11.004
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Human epidermal growth factor receptor 2 (HER2) is a prognostic biomarker and therapeutic target in carci-nomas of the breast, stomach and colon. In 2018, clinical trial data confirmed the prognostic and predictive role of HER2 in uterine serous carcinoma, with a demonstrated survival benefit from combined chemotherapy and anti-HER2 targeted therapy in patients with advanced or recurrent disease. Approximately one-third of uterine serous carcinomas demonstrate HER2 protein over-expression and/or gene amplification and HER2 immu-nohistochemistry, supplemented by in situ hybridisation in equivocal cases, is fast becoming a reflex ancillary test at time of diagnosis. The potential role of HER2 in gynae-cological tumours other than uterine serous carcinoma is yet to be firmly established. With the advent of personal-ised medicine, routine tumour sequencing and pursuit of targeted therapies, this is a field currently under active investigation. Emerging data suggest triaging endometrial carcinomas for HER2 analysis based on molecular clas-sification may be superior to histotype-based testing, with copy-number high/p53 mutant tumours enriched for HER2 overexpression or amplification. Accordingly, many carci-nosarcomas and a subset of clear cell and high-grade endometrioid carcinomas may be eligible for HER2 targeted therapy, although any clinical benefit in this context is currently undefined. For ovarian carcinomas, combined data support the role of HER2 as a prognostic biomarker, however its use as a therapeutic target is yet to be elucidated through clinical trials. In the cervix, reported rates of HER2 overexpression vary and are generally low, and currently there is insufficient evidence to justify routine HER2 testing in this context. Limited data suggest HER2 holds promise as a prognostic and predictive biomarker in vulvar Paget disease. Future clinical trials, with pathologist input to develop and refine site-specific scoring criteria, are required to establish what role HER2 might play more broadly in gynaecological cancer care.
引用
收藏
页码:8 / 18
页数:11
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