p300 (histone acetyltransferase) biomarker predicts prostate cancer biochemical recurrence and correlates with changes in epithelia nuclear size and shape

Abstract

Background: p300 impacts the transcription of several genes involved in key pathways critical to PCa progression. Therefore, we evaluated the prognostic value of p300 expression and its correlation with nuclear alterations seen in tumor cells in men with long-term follow-up after radical prostatectomy (RP).

Methods: NCI Cooperative Prostate Cancer Tissue Resource tissue microarray cores of 92 RP cases (56 non-recurrences and 36 PSA recurrences) were utilized for the study. p300 expression was assessed by quantitative immunohistochemistry and nuclear alterations in Feulgen-stained nuclei were evaluated by digital image analysis using the AutoCyte Pathology Workstation. Cox proportional hazards regression, Spearman's rank correlation, and Kaplan-Meier plots were employed to analyze the data.

Results: p300 expression significantly correlated with nuclear alterations seen in tumor cells; specifically with circular form factor (P = 0.012) and minimum feret (P = 0.048). p300 expression in high grade tumors (Gleason score >or=7) was significantly higher compared to low grade tumors (Gleason score <7) [17.7% versus 13.7%, respectively, P = 0.03]. TNM stage, Gleason score, and p300 expression were univariately significant in the prediction of PCa biochemical recurrence-free survival (P <or= 0.05). p300 expression remained significant in the multivariate model (P = 0.03) while Gleason score showed a trend toward significance (P = 0.06). Patients with a Gleason score >or=7 and p300 expression >24% showed the highest risk for PCa biochemical recurrence (P = 0.002).

Conclusions: p300 expression correlates with nuclear alterations seen in tumor cells and has prognostic value in predicting long-term PCa biochemical recurrence-free survival.

Figure 1

Kaplan-Meier plots showing ability of Gleason score (A), pathological stage (B), p300 expression (C), and Gleason score & p300 combined (D) to predict biochemical recurrence free survival. Logrank test and Logrank trend test were used to test equality of survivor functions across two groups and three ordered groups respectively.