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