Ductal adenocarcinoma (DCa) of the prostate is a rare cancer with poor prognosis, but the pathogenesis of DCa has not been elucidated and no useful biomarkers have been established. We reported that genomic profiling of Japanese DCa patients revealed that TP53 and RB1 mutations occur frequently more than western countries and that patients with p53 or RB1 mutations have a worse prognosis than those without mutations. However, due to the limited laboratory facilities and the cost of genomic analysis, it is impractical to analyze all patients. The aim of this study was to investigate the usefulness of p53 immunohistochemistry (IHC) staining as a surrogate prognostic biomarker in DCa.

Clinical and histological records from our hospitals were searched for radical prostatectomy, transurethral resection of the prostate, and prostate needle biopsy specimens with a DCa component in the past 16 years. We identified 43 patients diagnosed with DCa, and 30 patients were included in this study, for whom we were able to perform p53 IHC staining using formalin-fixed paraffin-embedded sections. Abnormal staining pattern of p53 were classified by dedicated uropathologist as overexpression, null mutant, or cytoplasmic expression. Genomic profiling was performed using the FoundationOne CDx or PleSSision testing platforms in 20 of the 30 patients. The correlation between the results of each method was analyzed, and the mutation-positive concordance rate was evaluated.

Twelve patients (40.0%) had pure type cancer, while 18 patients (60.0%) had a mixed type cancer with acinar adenocarcinoma. Six patients (20.0%) died of DCa during the median follow-up period of 29.3 months. The p53 IHC showed 8 cases of overexpression (26.7%), 3 cases of null mutant (10.0%), 0 cases of cytoplasmic expression (0.0%), and 19 cases of wild type (63.3%). Of the 20 cases for which genomic analysis was available, 5 (25.0%) were positive for TP53 mutations, 3 were missense mutations and 2 were nonsense mutations. All 5 mutation-positive cases were classified as overexpression on p53 IHC staining, and all 15 mutation-negative cases were wild type, with a mutation concordance rate of 100%.

Conclusion: Both mutation-positive and mutation-negative predictive value were 100%, indicating that TP53 mutations in Japanese DCa patients can be accurately detected by p53 IHC staining as a surrogate prognostic biomarker. These results suggest that p53 IHC staining may contribute to future multicenter, multi-case studies in terms of simplicity and versatility.