Overexpression of cyclin‐dependent kinase 4 protein in extramammary Paget's disease

Urata, Kazumi; Kajihara, Ikko; Myangat, Tselmeg Mijiddorj; Tasaki, Yukino; Maeda‐Otsuka, Saki; Sawamura, Soichiro; Yamada‐Kanazawa, Saori; Sakamoto, Ryoko; Makino, Katsunari; Aoi, Jun; Igata, Toshikatsu; Makino, Takamitsu; Masuguchi, Shinichi; Fukushima, Satoshi; Jinnin, Masatoshi; Ihn, Hironobu

doi:10.1111/1346-8138.14858

Cited by 13 publications

(16 citation statements)

References 15 publications

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“…As previously reported ( 34 ), neither CDK4 nor cyclin D1 was observed in the epidermis. CK7 was stained simultaneously to distinguish EMPD tumor cells.…”

Section: Resultssupporting

confidence: 79%

“…Although the overexpression of CDK4 and cyclin D1 is also observed in EMPD tumor cells ( 34 , 44 , 45 ), the correlation between their expression and patients’ prognosis has not been elucidated. In this study, we retrospectively reviewed 110 patients with EMPD, and assessed the associations between CDK4/cyclin D1 expression and survival.…”

Section: Discussionmentioning

confidence: 99%

“…All formalin-fixed (24 h in 10% buffered formalin), paraffin-embedded EMPD tissues were obtained from the archives of Kyushu University Hospital. Immunohistochemical staining was performed as reported previously with slight modifications ( 34 ). Tissue samples were cut into 4 µm sections.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, CDK4/6 inhibitors are currently widely used for the treatment of breast cancer, and their therapeutic value in this disease context has attracted significant attention (30)(31)(32)(33). Regarding EMPD, a recent report (34) suggested that CDK4 and cyclin D1 are overexpressed in EMPD tumor cells. However, the impact of their expression on prognosis has not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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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“…As previously reported ( 34 ), neither CDK4 nor cyclin D1 was observed in the epidermis. CK7 was stained simultaneously to distinguish EMPD tumor cells.…”

Section: Resultssupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…Immunohistochemistry was conducted with a primary antibody against TEM8 antibody (ab21270; Abcam, Cambridge, UK), as described previously. 4 We determined whether angiosarcoma cells have upregulated TEM8 protein levels when compared with senile angioma tissue and normal vessel cells by performing immunohistochemical staining. TEM8 protein was strongly expressed in angiosarcoma tissues when compared with senile angioma tissue and normal vessel cells (Figure 1a).…”

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confidence: 99%

Overexpression of tumor endothelial marker 8 protein predicts poor prognosis in angiosarcoma

Kusaba

Kajihara

Sakamoto

et al. 2021

The Journal of Dermatology

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Tumor angiogenesis is a key component that supports tumor growth. Tumor endothelial cells (TEC) are genetically and functionally different from normal endothelial cells (NEC). The biological characteristics of TEC are chromosomal instability, ability to proliferate/migrate, and resistance to anticancer drugs. 1 F I G U R E 1 (a) Representative images of immunohistochemistry of tumor endothelial marker (TEM)8 in normal vessels, senile angioma and angiosarcoma. TEM8 is overexpressed in the cytoplasm (not on the cell membrane) of angiosarcoma cells. Keratinocytes and lymphocytes were not stained with anti TEM8 antibody (internal negative control). (b) Representative images of stained tissues classified according to the immunohistochemical intensity of TEM8 (high or low). (c) Kaplan-Meier curves for overall survival of patients with angiosarcoma categorized according to the MUC16 immunoreactivity. Mantel-Cox log-rank test was conducted to search the meaning of TEM8 protein expression levels

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Extramammary Paget Disease: a Therapeutic Challenge, for a Rare Entity

et al. 2023

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Purpose of Review Extramammary Paget disease (EMPD) is a rare entity which is more frequently localized at the vulva, though it only accounts for 1–2% of vulvar neoplasms. It is a primary cutaneous adenocarcinoma whose cell of origin is still a matter of controversy: it can either arise from apocrine/eccrine glands or from stem cells. The diagnosis demands a biopsy and entails a histopathological analysis by which cells show similar characteristics as breast Paget disease. Recent Findings Treatment approach can entail surgery, radiotherapy, photodynamic therapy, systemic chemotherapy, and topical chemotherapy. For metastatic disease, many different chemotherapy regimens have been explored and even targeted therapy can play an important role in this disease. Since almost 30–40% of patients overexpress HER-2, trastuzumab and anti-HER-2 therapies can be employed in this setting. Summary Due to its low incidence, there is almost no specific evidence on therapeutic interventions for this disease. Thus, there is a neat unmet need for molecular characterization of EMPD and diagnostic tools that allow clinicians to guide treatment both in the early and in the advanced disease settings. In this review, we aim to summarize available evidence about diagnosis and treatment of EMPD, both localized and metastatic, and to provide a comprehensive analysis that may help clinicians for therapeutic decisions.

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Overexpression of cyclin‐dependent kinase 4 protein in extramammary Paget's disease

Cited by 13 publications

References 15 publications

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

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

Overexpression of tumor endothelial marker 8 protein predicts poor prognosis in angiosarcoma

Extramammary Paget Disease: a Therapeutic Challenge, for a Rare Entity

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