Penile squamous cell carcinoma (pSCC) severely impairs quality of life, yet reliable prognostic factors for lymph node metastasis (LNM) and survival remain incompletely defined. Existing LNM detection is invasive and risky, while prior TP53/p53-related pSCC studies are limited by small samples and conflicting results.
We analyzed p53 protein expression via IHC in a single-center retrospective pSCC cohort, combined with a systematic review and meta-analysis to validate TP53/p53 alterations' prognostic value for LNM, overall survival (OS), and cancer-specific survival (CSS).
In our single-center cohort, p53 mutant-pattern expression was associated with increased LNM risk (OR = 7.56, 95%CI = 1.48-38.52), inferior OS (HR = 6.15, 95%CI = 1.78-21.13), and poorer CSS (HR = 7.92, 95%CI = 1.99-31.45). These nominally significant associations with wide confidence intervals highlight the need for large-scale investigations; accordingly, we conducted a meta-analysis confirming that aberrant p53/TP53 status correlates with elevated LNM (pooled OR = 2.90, 95%CI = 1.89-4.44), inferior OS (pooled HR = 1.79, 95%CI = 1.31-2.44), and shorter CSS (pooled HR = 2.90, 95%CI = 1.55-5.42).
TP53 genetic status and p53 protein expression are consistently associated with LNM and survival outcomes, supporting a prognostic role in penile squamous cell carcinoma (pSCC). These associations are validated in a Chinese pSCC cohort and further quantify via comprehensive meta-analysis in this understudied rare malignancy. These findings highlight the potential of TP53/p53 assessment to inform future personalized management strategies for pSCC, pending formal validation of its clinical utility.
This study, integrating a single-center Chinese cohort validation with the first multi-source pooled analysis jointly quantifying the prognostic value of both TP53 genetic status and p53 protein expression in pSCC, addresses the critical gap of insufficient high-powered, integrated evidence for this potential prognostic biomarker, provides a consolidated evidence base for risk stratification in this rare malignancy, and informs the design of subsequent prospective validation studies.
Urologic oncology. 2026 Jul 23 [Epub ahead of print]
Zijian Cai, Hongtao Jin, Yepeng Guo, Desi Chen, Gaowei Huang, Xin Jiang, Jingjin Liu, Bo-Nan Chen, Xueqi Zhang, Zhaohui Chen, Zaishang Li
Department of Urology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China; Department of Urology, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China; Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital, Shenzhen, China., Department of Pathology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China; Department of Pathology, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China., Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital, Shenzhen, China; Department of Geriatrics, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China; Department of Geriatrics, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China., Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China; Department of State Key Laboratory of Digestive Disease Research, CUHK-Shenzhen Research Institute, Shenzhen, China., Department of Urology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China; Department of Urology, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China; Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital, Shenzhen, China. Electronic address: ., Department of Urology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China; Department of Urology, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China; Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital, Shenzhen, China. Electronic address: .