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Nectin-4 expression in a subset of cutaneous adnexal carcinomas: A potential target for therapy with enfortumab
Woo Cheal Cho1, Rayan Saade1, Priyadharsini Nagarajan1
1Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Background:
Enfortumab vedotin (EV) is an antibody-drug conjugate directed against Nectin-4 that is used to treat urothelial carcinoma. Nectin-4 is inherently expressed in the skin and adnexal structures. Since therapeutic options for cutaneous adnexal carcinomas are limited, we sought to evaluate Nectin-4 expression in adnexal carcinomas and benign adnexal neoplasms to identify tumors that are potentially targetable with EV.
Methods:
Eight sebaceous carcinomas (seven periocular and one lymph node metastasis), eight digital papillary adenocarcinomas, seven squamoid eccrine ductal carcinomas, eight poromas, eight trichilemmomas, and seven sebaceous adenomas were subjected to immunohistochemical staining for anti-Nectin-4 antibody. H-scores for Nectin-4 expression were calculated.
Results:
Benign adnexal neoplasms had a significantly lower mean (±SD) Nectin-4 H-score (142.6 ± 39.1) than did the adnexal carcinomas (198 ± 90.8; p = 0.006). Nectin-4 was expressed in 91% (21/23) of adnexal carcinomas. Sebaceous carcinomas frequently exhibited high expression of Nectin-4 (88% [7/8]), with a mean (±SD) H-score (258.1 ± 58.4) significantly higher than those for digital papillary adenocarcinomas (197.5 ± 52.5; p = 0.035) and squamoid eccrine ductal carcinomas (131.4 ± 114.1; p = 0.031). Sebaceous carcinomas also had significantly higher H-scores than did sebaceous adenomas (186.4 ± 25.0; p = 0.013).
Conclusions:
Increased Nectin-4 expression in a subset of cutaneous adnexal carcinomas, particularly sebaceous carcinomas, reveals that EV is a potential therapeutic option for these tumors.
Insights
Enfortumab vedotin (EV) targets Nectin-4. This study found high Nectin-4 expression in cutaneous adnexal carcinomas, especially sebaceous carcinomas, suggesting EV as a potential treatment for these rare tumors.
Area of Science:
- Dermatopathology
- Oncology
- Molecular Biology
Background:
- Enfortumab vedotin (EV) is an antibody-drug conjugate targeting Nectin-4, approved for urothelial carcinoma.
- Nectin-4 is normally expressed in skin and adnexal structures.
- Limited therapeutic options exist for cutaneous adnexal carcinomas.
Purpose of the Study:
- To evaluate Nectin-4 expression in various adnexal carcinomas and benign neoplasms.
- To identify adnexal tumors potentially targetable with enfortumab vedotin.
Main Methods:
- Immunohistochemical staining for anti-Nectin-4 antibody was performed on 23 adnexal carcinomas and 15 benign adnexal neoplasms.
- Nectin-4 expression levels were quantified using H-scores.
- Statistical analysis compared Nectin-4 expression between tumor types and benign lesions.
Main Results:
- Adnexal carcinomas showed significantly higher Nectin-4 expression (H-score 198) than benign neoplasms (H-score 142.6; p=0.006).
- Nectin-4 was expressed in 91% of adnexal carcinomas.
- Sebaceous carcinomas exhibited the highest Nectin-4 expression (88%), with significantly higher H-scores than digital papillary adenocarcinomas, squamoid eccrine ductal carcinomas, and sebaceous adenomas.
Conclusions:
- Cutaneous adnexal carcinomas, particularly sebaceous carcinomas, demonstrate increased Nectin-4 expression.
- This finding supports enfortumab vedotin as a potential targeted therapy for a subset of these tumors.
