Identification and validation of TP53/p53 status as a prognostic marker in penile squamous cell carcinoma: Evidence from a cohort study and meta-analysis.

BACKGROUND

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.

METHODS

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).

RESULTS

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).

CONCLUSIONS

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.

IMPACT: 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.