scholarly journals Trop2 Expression in Extramammary Paget’s Disease and Normal Skin

2021 ◽  
Vol 22 (14) ◽  
pp. 7706
Author(s):  
Takamichi Ito ◽  
Keiko Tanegashima ◽  
Yuka Tanaka ◽  
Hiroki Hashimoto ◽  
Maho Murata ◽  
...  

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.

2020 ◽  
Vol 21 (16) ◽  
pp. 5891
Author(s):  
Maho Murata ◽  
Takamichi Ito ◽  
Yuka Tanaka ◽  
Yumiko Kaku-Ito ◽  
Masutaka Furue

Extramammary Paget’s disease (EMPD) is a rare skin cancer arising in the anogenital area. Most EMPD tumors remain dormant as in situ lesions, but the outcomes of patients with metastatic EMPD are poor because of the lack of effective systemic therapies. Nectin cell adhesion molecule 4 (NECTIN4) has attracted attention as a potential therapeutic target for some cancers. Urothelial cancer is one such cancer, and clinical trials of enfortumab vedotin, a drug-conjugated anti-NECTIN4 antibody, are ongoing. However, little is known regarding the role of NECTIN4 in EMPD. In this study, we conducted immunohistochemical analysis of NECTIN4 expression in 110 clinical EMPD samples and normal skin tissue. In normal skin, positive signals were observed in epidermal keratinocytes (particularly in the lower part of the epidermis), eccrine and apocrine sweat glands, inner and outer root sheaths, and matrix of the hair follicles. The most EMPD lesions exhibited strong NECTIN4 expression, and high NECTIN4 expression was significantly associated with increased tumor thickness, advanced TNM stage, and worse disease-specific survival. These results support the potential use of NECTIN4-targeted therapy for EMPD. Our report contributes to the better understanding of the pathobiology of NECTIN4 in the skin and the skin-related adverse effects of NECTIN4-targeted therapy.


2016 ◽  
Vol 9 (1) ◽  
pp. 6-10 ◽  
Author(s):  
Yuki Yoshihara ◽  
Munenari Itoh ◽  
Yoshimasa Nobeyama ◽  
Hidemi Nakagawa

Extramammary Paget's disease (EMPD) is an uncommon cutaneous adenocarcinoma arising from the apocrine glands within the epidermis or underlying skin appendages in the anogenital and axillary regions. Surgical excision is basically performed as a treatment for EMPD. However, therapeutic options for EMPD in an advanced stage are limited. Herein, we report the case of a Japanese woman with advanced EMPD successfully controlled by monthly but not weekly docetaxel therapy. We also demonstrate the possibility that a monthly regimen of docetaxel is a more effective and optimal schedule than a weekly one through this case report.


2014 ◽  
Vol 8 ◽  
pp. CMO.S13107 ◽  
Author(s):  
Derek Isrow ◽  
Karlos Z. Oregel ◽  
Javier Cortes ◽  
Henry Gomez ◽  
Clara Milikowski ◽  
...  

Extramammary Paget's disease (EMPD) is a rare intraepithelial malignancy arising in areas rich in apocrine glands, such as the perineum, vulva, axilla, scrotum, and penis. We describe the case of a man in his 50s who initially presented with a small eczematous lesion on his right groin, treated with topical ointments for eczema, until excisional biopsy of lesion unequivocally revealed invasive EMPD. Despite aggressive surgical interventions, his disease progressed to involve the scrotum and penis. Deemed unresectable, the patient was treated with systemic chemotherapy with minimal response. The rarity of EMPD, especially of the penis and scrotum, warrants an educated eye and heightened index of suspicion when dealing with eczematous lesions in the groin in any person. Early biopsy and histological examination is crucial for early surgical intervention of the lesions. There are no guidelines available to treat locally advanced unresectable disease. In addition, further studies are needed to identify genetic defects underlying the pathogenesis of this rare disease, to help improve treatment strategies and decrease morbidity.


1984 ◽  
Vol 46 (5) ◽  
pp. 1118-1122 ◽  
Author(s):  
Yoshihisa FUJII ◽  
Nobuyuki SHIRAISHI ◽  
Etsuji MATSUNAGA ◽  
Susumu TAKAYASU ◽  
Toshitaka NAKAMURA

2007 ◽  
Vol 69 (3) ◽  
pp. 273-276
Author(s):  
Satoko KUMAZAWA ◽  
Kou DAN ◽  
Teiichi MASUDA ◽  
Kazunori URABE ◽  
Masutaka FURUE

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