AUTHOR=Hashimoto Hiroki , Kaku-Ito Yumiko , Oda Yoshinao , Ito Takamichi 

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

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.710378

DOI=10.3389/fonc.2021.710378

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>The 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.</p></sec><sec><title>Methods</title><p>We 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.</p></sec><sec><title>Results</title><p>Most 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, <italic>p</italic> &lt; 0.001). Tumor thickness (<italic>p</italic> = 0.0003) and the presence of regional lymph node metastasis (<italic>p</italic> = 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, <italic>p</italic> = 0.14).</p></sec><sec><title>Conclusion</title><p>The 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.</p></sec>