Expression of nectin-4 in germ-cell tumors.

e17009 Background: Nectin-4 is a cell adhesion molecule and therapeutic target in several malignancies, including urothelial carcinoma. However, its expression pattern in germ cell tumors (GCT) remains poorly characterized. Given the limited treatment options for refractory GCTs, and the urgent need for novel therapeutic options, we present a retrospective analysis of Nectin-4 expression on pathology samples from patients with GCT. Methods: Samples from 93 unique patients with GCT from Indiana University Simon Comprehensive Cancer Center from 2010-2022 were identified. Patients with both seminoma and non-seminoma were included. Nectin-4 staining was performed by IQVIA Laboratories using the non-commercially available anti-Nectin-4 antibody (clone M22-312B41.1). Results: Overall, 93 samples were identified, 5 subjects did not have sufficient tissue to complete Nectin 4 testing. Of 88 evaluable samples, 43 (48.8%) demonstrated Nectin-4 expression. Expression varied significantly by histology. Teratoma demonstrated the highest prevalence, with 33 of 38 cases (86.8%) positive, with frequent high levels of expression (17 of 33 exhibiting ≥20% neoplastic cell positivity). Seminoma showed infrequent expression (3 of 29, 10.3%). No expression was observed in pure embryonal carcinoma (0 of 8). Yolk sac tumors demonstrated variable expression (3 of 7, 42.8%). Mixed histology tumors showed expression in 66% (4 of 6). Nectin-4 positivity was observed across multiple anatomic sites, including retroperitoneal lymph nodes (RP LN), lung, mediastinum, kidney, ureter, and other lymph nodes (LN) and metastatic locations. Conclusions: Nectin-4 varies across histology in GCT. Teratoma has the highest expression of Nectin-4 while embryonal carcinoma appears to have the lowest expression. Expression was not site restricted. These findings suggest that Nectin-4 may represent a biologically relevant therapeutic target especially in patients with unresectable teratoma. Nectin-4 expression by histologic subtype and anatomic site in germ cell tumors. Histology Nectin 4 expression (%) Sites All 43/88 (48.8%) Teratoma 33/38 (86.8%) RP LN (22)Lung (5)Mediastinum (3)Neck (1)Pelvic LN (1)Kidney (1) Seminoma 3/29 (10.3%) RP LN (2)Testis (1) Yolk Sac 3/7 (42.8%) RP LN (1)Ureter (1)Mediastinum (1) Embryonal Carcinoma 0/8 (0%) N/A Mixed Histology 4/6 (66.6%) Testis (1)RP LN (1)Mediastinum (2)