Abstract
Extramammary Paget’s disease (EMPD) is a rare skin cancer arising in the apocrine gland-rich areas. Most EMPD tumors are dormant, but metastatic lesions are associated with poor outcomes owing to the lack of effective systemic therapies. Trophoblast cell surface antigen 2 (Trop2), a surface glycoprotein, has drawn attention as a potential therapeutic target for solid tumors. Sacituzumab govitecan, an antibody–drug conjugate of Trop2, has recently entered clinical use for the treatment of various solid cancers. However, little is known about the role of Trop2 in EMPD. In this study, we immunohistochemically examined Trop2 expression in 116 EMPD tissue samples and 10 normal skin tissues. In normal skin, Trop2 was expressed in the epidermal keratinocytes, inner root sheaths, and infundibulum/isthmus epithelium of hair follicles, eccrine/apocrine glands, and sebaceous glands. Most EMPD tissues exhibited homogeneous and strong Trop2 expression, and high Trop2 expression was significantly associated with worse disease-free survival (p = 0.0343). These results suggest the potential use of Trop2-targeted therapy for EMPD and improve our understanding of the skin-related adverse effects of current Trop2-targeted therapies such as sacituzumab govitecan.
Highlights
Accepted: 17 July 2021Extramammary Paget’s disease (EMPD) is a rare skin cancer that mainly affects apocrine sweat gland-rich areas in elderly people [1,2]
Trophoblast cell surface antigen 2 (Trop2), known as tumor-associated calcium signal transducer (Tacstd2), is a surface glycoprotein originally identified in human placental trophoblasts [15,16,17]
We examined the localization of Trop2 in normal skin and appendages to better understand the skin adverse effects of Trop2-targeting antibody–drug conjugate (ADC)
Summary
Accepted: 17 July 2021Extramammary Paget’s disease (EMPD) is a rare skin cancer that mainly affects apocrine sweat gland-rich areas in elderly people [1,2]. Primary EMPD arises as an intraepithelial neoplasm of the epidermis and can be distinguished from mammary. Paget’s disease (a type of breast cancer) and secondary EMPD (direct invasion from the visceral cancers including colorectal, vaginal, and urothelial cancers) clinically and immunohistochemically [1,4]. Most patients with EMPD have a good prognosis owing to the slow-growing nature of the disease given that tumors arise in the epidermis and remain dormant as in situ lesions for prolonged periods [1,7,8]. EMPD lesions show infiltrative erythema with crust and scale and clinically mimick many other benign inflammatory skin diseases including contact dermatitis, eczema, and superficial fungal infections, which leads to misdiagnosis or diagnostic delay [4].
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