Successful human epidermal growth receptor 2-targeted therapy beyond disease progression for 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.

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Case for diagnosis

Anais Brasileiros de Dermatologia ◽

10.1590/abd1806-4841.20132311 ◽

2013 ◽

Vol 88 (5) ◽

pp. 828-830 ◽

Cited By ~ 1

Author(s):

Andre Lencastre ◽

Joana Cabete ◽

Maria Margarida Apetato

Keyword(s):

Disease Progression ◽

Symptomatic Relief ◽

Paget’S Disease ◽

Paget's Disease ◽

Extramammary Paget’S Disease ◽

Total Excision ◽

Erythematous Plaque ◽

Rare Presentation ◽

Disease Free ◽

Extramammary Paget's Disease

An 83 year-old man was observed for an 8 year-long pruritic, erythematous plaque of the left axilla. He had been continuously medicated with topical antifungals and steroids with occasional symptomatic relief, but with disease progression. After a clinical and histological diagnosis of Extramammary Paget's Disease, a total excision with wide margins was performed. He remains disease-free 12 months after surgery. We report this rare presentation of Extramammary Paget's Disease on a male patient.

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

Frontiers in Oncology ◽

10.3389/fonc.2021.710378 ◽

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.

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Estrogen Receptor and Progesterone Receptor Positive Pigmented Extramammary Paget’s Disease of the Axilla Mimicking Melanoma: A Case Report and Review of the Literature

Journal of Clinical Research in Dermatology ◽

10.15226/2378-1726/7/4/001122 ◽

2020 ◽

Vol 7 (4) ◽

pp. 1-4

Author(s):

Chi Shyan Wang ◽

Hsuan Hsiang Chen ◽

Shih Hao Liu

Keyword(s):

Estrogen Receptor ◽

Progesterone Receptor ◽

Paget’S Disease ◽

Growth Factor Receptor ◽

Paget's Disease ◽

Extramammary Paget’S Disease ◽

Review Of The Literature ◽

Pigmented Lesions ◽

Epidermal Growth ◽

Extramammary Paget's Disease

Pigmented extramammary Paget’s disease (EMPD) is a rare variant which is often confused clinically and histologically with melanoma or other pigmented lesions. Herein, we describe a rare case of pigmented EMPD involving the axilla of a 40-year-old female thought initially to represent malignant melanoma clinically. Immunohistochemically, the neoplastic cells are positive for Estrogen Receptor (ER), Progesterone Receptor (PR), and weakly positive for Human Epidermal Growth Factor Receptor 2 (Her2). A review of the literature reveals that the pigmented variant of EMPD could be easily misdiagnosed as melanoma initially and additional confirmatory studies are almost always needed to confirm the diagnosis. The expression of ER and PR in pigmented EMPD is rarely mentioned previously. We believe it should be further investigated for the understanding of pathogenesis in pigmented EMPD and the potential role of adjuvant hormonal therapy. Keywords: Extramammary Paget’s Disease; Axilla; Estrogen Receptor; Progesterone Receptor

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