TROP2 Expression in Sebaceous and Sweat Gland Carcinoma

Abstract

Sebaceous carcinoma and sweat gland carcinoma (malignant tumors with apocrine and eccrine differentiation) are rare malignant skin adnexal tumors that differentiate toward sebaceous gland and eccrine and apocrine glands, respectively. Owing to the rarity of these carcinomas, standard treatments for advanced disease have not been established. Because the prognosis of patients with systemic metastasis is poor, a new treatment for these diseases is eagerly desired. Trophoblast cell surface antigen 2 (TROP2) and sacituzumab govitecan, an antibody–drug conjugate of TROP2, have attracted attention in the treatment of various solid tumors. In the current study, we immunohistochemically investigated TROP2 expression in 14 sebaceous carcinoma and 18 sweat gland carcinoma samples and found strong and relatively homogeneous TROP2 staining in both cancer types. The mean Histoscore, a semi-quantitative scoring ranging from 0 (negative) to 300, was 265.5 in sebaceous carcinoma and 260.0 in sweat gland carcinoma. These observations directly suggest that both sebaceous carcinoma and sweat gland carcinoma could be potentially treated with TROP2-targeted antibody–drug conjugates such as sacituzumab govitecan.

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

“…The mean H-score for the sebaceous carcinoma group in our study was 258.1, which is nearly identical to that seen in their study. 23 We further documented Nectin-4 expression in two other rare types of cutaneous adnexal carcinomas: digital papillary adenocarcinomas and squamoid eccrine ductal carcinomas. In our study, the level of Nectin-4 expression in these two adnexal carcinomas appeared to be significantly less than that in sebaceous carcinomas.…”

“…Previous studies have reported Nectin‐4 to be highly expressed in melanomas, 21 squamous cell carcinomas, 22 and extramammary Paget disease 14 . Most recently, Nectin‐4 was reported to be frequently expressed in sebaceous carcinomas and sweat gland carcinomas (types unspecified) 23 . Their study included 14 cases of sebaceous carcinoma and 18 cases of sweat gland carcinoma.…”

“…14 Most recently, Nectin-4 was reported to be frequently expressed in sebaceous carcinomas and sweat gland carcinomas (types unspecified). 23 Their study included 14 cases of sebaceous carcinoma and 18 cases of sweat gland carcinoma. They reported that the mean H-score for Nectin-4 expression was 259.4…”

“…Most, if not all, prior studies investigating immunohistochemical Nectin-4 expression largely focused on malignant neoplasms. Also, a prior study 23 promoting cell migration, proliferation, and survival. 27 One recurring pathway described in prior reports that seems to be activated by Nectin-4 in epithelial-derived cancers and melanomas alike is the phosphoinositide 3-kinase/Akt pathway.…”

Nail Apparatus Melanoma: Current Management and Future Perspectives

“…FDA-approved ADCs for solid tumors include trastuzumab emtansine and trastuzumab deruxtecan (anti-HER2 ADCs) for breast cancer, enfortumab vedotin (anti-NECTIN-4 ADC) for urothelial cancer, sacituzumab govitecan (anti-TROP-2 ADC) for breast cancer, and tisotumab vedotin (anti-tissue factor ADC) for cervical cancer. Interestingly, NECTIN-4 and TROP-2 are highly expressed in normal skin and its appendages, as well as in various skin cancers [ 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 ], and anti-NECTIN-4 ADC might be a candidate for unresectable skin cancers, including NAM. Several melanoma-specific ADCs are currently undergoing preclinical and clinical trials.…”