Abstract: PD71-11
Sources of Funding: CPDR Program HU0001 10-2-0002 to I.R.

Introduction

p53 has been widely studied in prostate cancer (CaP). Next-Gen Sequencing (NGS) studies of prostate tumors reveal that p53 mutations are frequently observed in castration resistant CaP genomes. Recently, Haffner et al. (JCI, 2013) reported data on a single patient with a p53 mutation in a primary, well differentiated tumor at time of radical prostatectomy (RP) that was linked to future metastatic lesions. Lymphatic vessel invasion (LI) has also been demonstrated to predict poor CaP outcomes. The study purpose was to evaluate independent and combined roles of p53 and LI status in predicting CaP progression in a RP patient cohort with long-term follow-up.

Methods

This retrospective RP cohort study was comprised of CaP patients (50 metastatic; 138 randomly sampled, non-metastatic) enrolled at the Walter Reed National Military Medical Center between 1993 and 2013. Representative sections of whole mounted RP specimens were examined. LI and p53 status were assessed using immunohistochemistry staining with Biocare Medical D2-40 & p53 Tumor Suppressor Protein monoclonal antibodies. In CaP index tumors, p53 status was evaluated as percent p53 positive (+) tumor cells divided by total index tumor area (0%, 1-5%, >5%). Kaplan Meier (KM) estimation curves were used to examine time to biochemical recurrence (BCR) and distant metastasis as a function of p53 and LI status.

Results

Of the 188 eligible patients, median age at RP and follow-up time were 60.4 and 12.7 years, respectively. Nearly half (49.2%) of tumors stained focally as p53+ while 26.6% of patients had evidence of LI. p53+ patients had higher pathologic T stage (61.6% p53+ vs. 38.4% p53-, p = 0.0068). In KM models, p53+ >5% alone predicted BCR (p = 0.0075) and distant metastasis (p = 0.0053). When p53 status was examined in combination with LI, the poorest CaP outcomes were observed for those jointly LI+/p53 >5% (Figure 1a-b, p < 0.0001).

Conclusions

p53 protein expression, alone and in combination with LI status, predicts CaP progression after RP. These data suggest that determination of p53 alterations is warranted for improved prognostication of CaP progression.

Funding

CPDR Program HU0001 10-2-0002 to I.R.