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

• Published in: The Prostate Vol. 68; no. 10; pp. 1097 - 1104
• Main Authors: Isharwal, Sumit, Miller, Michael C., Marlow, Cameron, Makarov, Danil V., Partin, Alan W., Veltri, Robert W.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2008; Wiley-Liss
• Subjects: Adult; Aged; biochemical recurrence; Biological and medical sciences; Biomarkers, Tumor - metabolism; Cell Nucleus Shape; Disease-Free Survival; Epithelial Cells - metabolism; Epithelial Cells - pathology; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Nephrology. Urinary tract diseases; p300 expression; p300-CBP Transcription Factors - metabolism; Predictive Value of Tests; Prognosis; Proportional Hazards Models; prostate cancer; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Acyltransferases; Andrology; Nephrology; Relapse; Urinary system disease; Shape; Prognosis; Prostate disease; Enzyme; biochemical recurrence; Transferases; Gynecology; Size; Biological marker; Biological indicator; Biochemistry; p300 expression; Malignant tumor; Epithelium; Histone acetyltransferase; Predictive factor; Male genital diseases; Prostate cancer; Cancer
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.20772

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 ≥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 ≤ 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 ≥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. Prostate 68:1097–1104, 2008. © 2008 Wiley‐Liss, Inc.