Abstract

<div>Abstract<p><b>Purpose:</b> The DNA replication licensing machinery is integral to the control of proliferation, differentiation, and maintenance of genomic stability in human cells. We have analyzed replication licensing factors (RLF), together with DNA ploidy status, to investigate their role in progression of penile squamous cell carcinoma and to assess their utility as novel prognostic tools.</p><p><b>Experimental Design:</b> In a cohort of 141 patients, we linked protein expression profiles of the standard proliferation marker Ki67 and the RLFs Mcm2 and geminin to clinicopathologic variables, ploidy status, and clinical outcome.</p><p><b>Results:</b> Increased Ki67, Mcm2, and geminin levels were each significantly associated with arrested tumor differentiation (<i>P</i> < 0.0001) and aneuploidy (<i>P</i> ≤ 0.01). Accelerated cell cycle progression was linked to increasing tumor size, stage, and depth of invasion. Aneuploid tumors significantly correlated with tumor grade (<i>P</i> < 0.0001). Biomarker expression and DNA ploidy status were significant predictors of locoregional disease progression [Mcm2 (<i>P</i> = 0.02), geminin (<i>P</i> = 0.02), Ki67 (<i>P</i> = 0.03), and aneuploidy (<i>P</i> = 0.03)] in univariate analysis. Importantly, aneuploidy was a strong independent prognosticator for overall survival (hazard ratio, 4.19; 95% confidence interval, 1.17-14.95; <i>P</i> = 0.03). Used in conjunction with conventional pathologic information, multiparameter analysis of these variables can stratify patients into low- or high-risk groups for disease progression (Harrell's c-index = 0.88).</p><p><b>Conclusions:</b> Our findings suggest that RLFs and tumor aneuploidy may be used as an adjunct to conventional prognostic indicators, identifying men at high risk of disease progression. Our results also identify the DNA replication initiation pathway as a potentially attractive therapeutic target in penile squamous cell carcinoma. (Clin Cancer Res 2009;15(23):7335–44)</p></div>

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.