Woo Cheal Cho, Rayan Saade, Priyadharsini Nagarajan, Phyu P. Aung, Denái R. Milton, Mario L. Marques‐Piubelli, Courtney Hudgens, Debora Ledesma, Kelly Nelson, Doina Ivan, Miao Zhang, Carlos A. Torres‐Cabala, Matthew Campbell, Omar Alhalabi, Victor G. Prieto, Ignacio I. Wistuba, Bita Esmaeli, Jonathan L. Curry

Nectin‐4 expression in a subset of cutaneous adnexal carcinomas: A potential target for therapy with enfortumab vedotin

  • Dermatology
  • Histology
  • Pathology and Forensic Medicine
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AbstractBackgroundEnfortumab 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.MethodsEight 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.ResultsBenign 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).ConclusionsIncreased Nectin‐4 expression in a subset of cutaneous adnexal carcinomas, particularly sebaceous carcinomas, reveals that EV is a potential therapeutic option for these tumors.

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