表达 HER2 的宫颈鳞状细胞癌的分子和临床病理学特征。

IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY International Journal of Gynecological Pathology Pub Date : 2024-10-31 DOI:10.1097/PGP.0000000000001068
Rachelle P Mendoza, Madhurya Ramineni, Kristina Doytcheva, Elmer C Gabutan, Raavi Gupta, Cole Miller, Donghyuk Choi, Anusha Vemuri, Renee Briese, Lisa Brannon, Anum Shahid, Kristin Petras, Minhaz Ud Dean, Carrie Fitzpatrick, Jeremy Segal, Peng Wang, Ricardo R Lastra
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引用次数: 0

摘要

宫颈癌中的 HER2 扩增与较差的临床预后和对 HER2 抑制剂的潜在有利反应有关。HER2 受体免疫组化是公认的 HER2 扩增替代检测方法,但目前还没有针对宫颈癌的标准化评分系统。在这项研究中,我们使用荧光原位杂交(FISH)和分子方法研究了宫颈鳞状细胞癌中的 HER2 过表达,并将其与 HER2 扩增联系起来。对72例人乳头状瘤病毒相关宫颈癌病例进行了回顾性研究,并对至少2个具有代表性的肿瘤切片进行了HER2染色。采用2018年美国临床肿瘤学会/美国病理学家学会乳腺癌标准进行HER2评分,对表达不明确(2+)至阳性(3+)的病例采用FISH和下一代测序分析HER2扩增。患者平均年龄为 50 岁(范围:27-85 岁),大多数患者为非裔美国人(73.6%),确诊时处于 FIGO I 期(65.3%)。19例(26.4%)HER2表达不明确,4例(5.5%)呈阳性表达。4例阳性表达病例中,有3例的肿瘤足以进行FISH检查,且3例均有扩增。3例表达不明确的病例在FISH中显示出HER2多体,但没有一例显示出HER2扩增。临床分期晚、肿瘤分级高和区域淋巴结转移与HER2过表达和HER2扩增显著相关。对3个HER2扩增肿瘤进行的新一代测序显示,包括CD274、JAK2、BIRC3和ERBB2在内的多个基因发生了扩增,PIK3CA也发生了错义突变。总之,HER2 免疫组化是宫颈癌 HER2 扩增的可靠预测指标。
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Molecular and Clinicopathologic Characterization of HER2-overexpressed Squamous Cell Carcinoma of the Cervix.

HER2 amplification in cervical cancer has been associated with worse clinical prognosis and a potential favorable response to HER2 inhibitors. Immunohistochemistry for the HER2 receptor is a universally accepted surrogate test for HER2 amplification, but no standardized scoring system currently exists for cervical carcinomas. In this study, we investigated HER2 overexpression in cervical squamous cell carcinoma and correlated it with HER2 amplification using fluorescence in situ hybridization (FISH) and molecular methods. Seventy-two cases of human papillomavirus-associated cervical cancer were retrospectively reviewed, and at least 2 representative tumor sections were stained for HER2. HER2 scoring was performed using the 2018 American Society of Clinical Oncology/College of American Pathologist breast cancer criteria, and cases with equivocal (2+) to positive (3+) expression were analyzed for HER2 amplification using FISH and next-generation sequencing. The average patient age was 50 yrs (range: 27-85 yr), with most patients being African American (73.6%) and diagnosed at FIGO stage I (65.3%). Nineteen (26.4%) had equivocal HER2 expression and 4 (5.5%) showed positive expression. Three of the 4 cases with positive expression had enough tumors for FISH, and all 3 were amplified. Three cases with equivocal expression showed HER2 polysomy on FISH, and none showed HER2 amplification. Late clinical stage, high tumor grade, and regional lymph node metastasis were significantly correlated with HER2 overexpression and HER2 amplification. Next-generation sequencing of the 3 HER2-amplified tumors showed amplification of various genes, including CD274, JAK2, BIRC3, and ERBB2, and a PIK3CA missense mutation. In summary, HER2 immunohistochemistry is a reliable predictive marker of HER2 amplification in cervical cancer.

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来源期刊
CiteScore
3.90
自引率
12.50%
发文量
154
审稿时长
6-12 weeks
期刊介绍: International Journal of Gynecological Pathology is the official journal of the International Society of Gynecological Pathologists (ISGyP), and provides complete and timely coverage of advances in the understanding and management of gynecological disease. Emphasis is placed on investigations in the field of anatomic pathology. Articles devoted to experimental or animal pathology clearly relevant to an understanding of human disease are published, as are pathological and clinicopathological studies and individual case reports that offer new insights.
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