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. 2021 Jul 29:11:710378.
doi: 10.3389/fonc.2021.710378. eCollection 2021.

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

Hiroki Hashimoto  1 , Yumiko Kaku-Ito  1 , Yoshinao Oda  2 , Takamichi Ito  1
Affiliations

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

Hiroki Hashimoto et al. Front Oncol. .

Abstract

Background: 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.

Methods: 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.

Results: 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, 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).

Conclusion: 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.

Keywords: CDK4; CDK4/6 inhibitor; cyclin D1; extramammary Paget’s disease; prognostic factor; targeted therapy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A–D) Representative histopathological images of CDK4, cyclin D1, and cytokeratin 7 staining in EMPD. H-scores for CDK4 were: (A) 153, (B) 121, (C) 185, and (D) 200, and H-scores for cyclin D1 were: (A) 121, (B) 90, (C) 106, and (D) 195.
Figure 2
Figure 2
Scatter diagram showing the positive correlation between CDK4 and cyclin D1 expression (r = 0.54, p < 0.001).
Figure 3
Figure 3
Kaplan-Meier disease-specific survival curves of 42 patients with invasive EMPD stratified by CDK4/cyclin D1 expression.
See this image and copyright information in PMC

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