Assessment of trophoblast cell-surface antigen 2 (TROP2) and nectin-4 expression in choriocarcinoma

IF 2.7 2区医学 Q2 PATHOLOGY

Human pathology Pub Date : 2025-05-01 DOI:10.1016/j.humpath.2025.105815

Burak Tekin , John C. Cheville , Dragana Milosevic , Michael McCarthy , Rumeal D. Whaley , Loren Herrera Hernandez , Rafael E. Jimenez , Vidit Sharma , Bradley C. Leibovich , Stephen A. Boorjian , Brian A. Costello , Lance C. Pagliaro , Sounak Gupta

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引用次数: 0

Abstract

Objectives

Choriocarcinoma is associated with high mortality in multiply relapsed patients. Herein, we assessed immunohistochemistry (IHC) expression of TROP2 and nectin-4 in choriocarcinoma and other germ cell tumors (GCT), as antibody drug conjugates (ADCs) targeting these markers are entering the therapeutic landscape of many tumors.

Methods

Archival cases of choriocarcinoma and controls (non-choriocarcinoma GCT) were evaluated for TROP2 and nectin-4 IHC, performed on whole-slide sections, and results were quantified using H-scores (range: 0–300) based on membranous staining.

Results

The cohort included 20 primary GCT and 15 metastases from 34 patients. Of these, 18 specimens were choriocarcinoma (3 primary and 15 metastases), including six women with gestational choriocarcinoma. Median TROP2 and nectin-4 H-scores in choriocarcinomas were 22.5 and 60, respectively. For TROP2 and nectin-4, H-scores>200 were noted in 27.8% of patients, each. There was no correlation between serum beta-hCG levels measured within 2 weeks prior to specimen collection or peak serum beta-hCG levels and TROP2 or nectin-4 expression. The control group consisted of seminoma (n = 10); yolk sac tumor (n = 9), embryonal carcinoma (n = 10), postpubertal teratoma (n = 5), and spermatocytic tumor (n = 2). The median TROP2 H-scores for embryonal carcinoma, teratoma, and yolk sac tumor were 35, 30, and 15, respectively, and 0 for the remainder. The median nectin-4 H-score was 0 for all control group categories. Choriocarcinomas had a higher nectin-4 H-score compared to the control group (p < 0.001).

Conclusions

Given the high TROP2 and nectin-4 expression in a subset of choriocarcinoma, ADCs targeting these biomarkers may be a promising therapeutic approach for these tumors, pending additional validation.

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滋养细胞表面抗原2 （TROP2）和连接蛋白4在绒毛膜癌中的表达。

目的：绒毛膜癌与多次复发患者的高死亡率相关。在此，我们评估了绒毛膜癌和其他生殖细胞肿瘤（GCT）中TROP2和nectin-4的免疫组织化学（IHC）表达，因为靶向这些标志物的抗体药物偶联物（adc）正在进入许多肿瘤的治疗领域。方法：对绒毛膜癌和对照组（非绒毛膜癌GCT）的档案病例进行TROP2和nectin-4免疫组化评估，在整片切片上进行，并使用基于膜染色的h评分（范围：0-300）对结果进行量化。结果：该队列包括来自34例患者的20例原发性GCT和15例转移性GCT。其中，18例为绒毛膜癌（3例原发，15例转移），包括6例妊娠期绒毛膜癌。绒毛膜癌的中位TROP2和nectin-4 h评分分别为22.5和60。对于TROP2和nectin-4, 27.8%的患者h评分均为bb0 200。在标本采集前2周内测量的血清β - hcg水平或血清β - hcg水平峰值与TROP2或nectin-4表达之间没有相关性。对照组为精原细胞瘤（n=10）；卵黄囊瘤（9例）、胚胎癌（10例）、青春期后畸胎瘤（5例）、精细胞瘤（2例）。胚胎癌、畸胎瘤和卵黄囊瘤的TROP2 h评分中位数分别为35、30和15，其余为0。所有对照组的中位连线素-4 h评分均为0。与对照组相比，绒毛膜癌的连接蛋白-4 h值更高(结论：考虑到在一部分绒毛膜癌中TROP2和连接蛋白-4的高表达，针对这些生物标志物的adc可能是一种有希望的治疗这些肿瘤的方法，有待进一步验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human pathology 医学-病理学

CiteScore

5.30

自引率

6.10%

发文量

206

审稿时长

21 days

期刊介绍： Human Pathology is designed to bring information of clinicopathologic significance to human disease to the laboratory and clinical physician. It presents information drawn from morphologic and clinical laboratory studies with direct relevance to the understanding of human diseases. Papers published concern morphologic and clinicopathologic observations, reviews of diseases, analyses of problems in pathology, significant collections of case material and advances in concepts or techniques of value in the analysis and diagnosis of disease. Theoretical and experimental pathology and molecular biology pertinent to human disease are included. This critical journal is well illustrated with exceptional reproductions of photomicrographs and microscopic anatomy.