scholarly journals NECTIN4 Expression in Extramammary Paget’s Disease: Implication of a New Therapeutic Target

2020 ◽  
Vol 21 (16) ◽  
pp. 5891
Author(s):  
Maho Murata ◽  
Takamichi Ito ◽  
Yuka Tanaka ◽  
Yumiko Kaku-Ito ◽  
Masutaka Furue
Keyword(s):  
Targeted Therapy ◽  
Therapeutic Target ◽  
Normal Skin ◽  
Paget’S Disease ◽  
Paget's Disease ◽  
Hair Follicles ◽  
Sweat Glands ◽  
Epidermal Keratinocytes ◽  
Extramammary Paget’S Disease ◽  
Extramammary Paget's Disease

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.

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 ◽  
...  
Keyword(s):  
Normal Skin ◽  
Paget’S Disease ◽  
Disease Free Survival ◽  
Paget's Disease ◽  
Hair Follicles ◽  
Surface Glycoprotein ◽  
Epidermal Keratinocytes ◽  
Extramammary Paget’S Disease ◽  
Apocrine Glands ◽  
Extramammary Paget's Disease

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.

scholarly journals CDK4: A Novel Therapeutic Target for Extramammary Paget’s Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Hiroki Hashimoto ◽  
Yumiko Kaku-Ito ◽  
Yoshinao Oda ◽  
Takamichi Ito
Keyword(s):  
Targeted Therapy ◽  
Cyclin D1 ◽  
Therapeutic Target ◽  
Regional Lymph Node ◽  
Paget’S Disease ◽  
Paget's Disease ◽  
Extramammary Paget’S Disease ◽  
The Impact ◽  
Cdk4 Expression ◽  
Extramammary Paget's Disease

BackgroundThe outcome of extramammary Paget’s disease (EMPD) is poor when it progresses to metastasis because of the lack of effective systemic therapies. Recently, CDK4-targeted therapy has attracted attention as a potential therapeutic target for some cancers. The aim of this study was to analyze the impact of CDK4 expression on the survival of patients with EMPD.MethodsWe retrospectively reviewed 110 patients with EMPD. We conducted immunohistochemical analysis of CDK4 and cyclin D1 expression, and assessed the association between their expression and survival.ResultsMost EMPD lesions (108/110, 98.2%) were positive for CDK4 staining and there was a positive correlation between CDK4 expression and cyclin D1 expression (r = 0.54, p < 0.001). Tumor thickness (p = 0.0003) and the presence of regional lymph node metastasis (p = 0.015) were significantly associated with high CDK4 expression. Regarding invasive EMPD, the multivariate analysis did not show the correlation between the expression of CDK4/cyclin D1 and survival outcomes (HR: 3.14, p = 0.14).ConclusionThe overexpression of CDK4 was identified as a major risk factor for disease progression. CDK4-targeted therapy could thus be a novel treatment option for unresectable EMPD.

Successful human epidermal growth receptor 2-targeted therapy beyond disease progression for extramammary Paget’s disease

2016 ◽  
Vol 34 (3) ◽  
pp. 394-396 ◽  
Author(s):  
Satomi Watanabe ◽  
Masayuki Takeda ◽  
Takayuki Takahama ◽  
Tsutomu Iwasa ◽  
Junji Tsurutani ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Disease Progression ◽  
Paget’S Disease ◽  
Paget's Disease ◽  
Extramammary Paget’S Disease ◽  
Epidermal Growth ◽  
Extramammary Paget's Disease

scholarly journals Overexpression of Janus kinase 2 protein in extramammary Paget’s disease

2021 ◽  
Author(s):  
Saki Otsuka-Maeda ◽  
Myangat Tselmeg Mijiddorj ◽  
Ikko Kajihara ◽  
Ryoko Sakamoto ◽  
Saori Yamada-Kanazawa ◽  
...  
Keyword(s):  
Distant Metastasis ◽  
Therapeutic Target ◽  
Paget’S Disease ◽  
Paget's Disease ◽  
Janus Kinase ◽  
Extramammary Paget’S Disease ◽  
Janus Kinase 2 ◽  
Promising Therapeutic Target ◽  
The Relationship ◽  
Extramammary Paget's Disease

Abstract Extramammary Paget’s disease is a rare malignant tumor of the skin that occurs primarily in the genitocrural region. Although the prognosis of extramammary Paget’s disease with distant metastasis is poor, an effective therapy has not been established. Because Janus kinase 2 has attracted attention as a therapeutic target in several cancers, we investigated the expression of the Janus kinase 2 protein and the relationship between its level of expression and clinical significance in 53 patients with extramammary Paget’s disease in our hospital. Immunohistochemistry showed that most extramammary Paget’s disease tissues were positive for Janus kinase 2 (50/53, 94.3%), and the immunostaining intensity of Janus kinase 2 was correlated with the degree of invasiveness, lymph node metastasis and distant metastasis. Based on these findings, Janus kinase 2 may be a promising therapeutic target in extramammary Paget’s disease.

Four cases of extramammary Paget's disease - A topographic study.

1984 ◽  
Vol 46 (5) ◽  
pp. 1118-1122 ◽  
Author(s):  
Yoshihisa FUJII ◽  
Nobuyuki SHIRAISHI ◽  
Etsuji MATSUNAGA ◽  
Susumu TAKAYASU ◽  
Toshitaka NAKAMURA
Keyword(s):  
Paget’S Disease ◽  
Paget's Disease ◽  
Extramammary Paget’S Disease ◽  
Extramammary Paget's Disease
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