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Expression of E6AP and PML predicts for prostate cancer progression and cancer-specific death


BACKGROUND: The promyelocytic leukemia (PML) tumor suppressor plays an important role in the response to a variety of cellular stressors and its expression is downregulated or lost in a range of human tumors. We have previously shown that the E3 ligase E6-associated protein (E6AP) is an important regulator of PML protein stability but the relationship and clinical impact of PML and E6AP expression in prostatic carcinoma is unknown. METHODS: E6AP and PML expression was assessed in tissue microarrays from a phase I discovery cohort of 170 patients treated by radical prostatectomy for localized prostate cancer (PC). Correlation analysis was carried out between PML and E6AP expression and clinicopathological variates including PSA as a surrogate of disease recurrence. The results were confirmed in a phase II validation cohort of 318 patients with associated clinical recurrence and survival data. RESULTS: Survival analysis of the phase I cohort revealed that patients whose tumors showed reduced PML and high E6AP expression had reduced time to PSA relapse (P = 0.012). This was confirmed in the phase II validation cohort where the expression profile of high E6AP/low PML was significantly associated with reduced time to PSA relapse (P < 0.001), clinical relapse (P = 0.016) and PC-specific death (P = 0.014). In multivariate analysis, this expression profile was an independent prognostic indicator of PSA relapse and clinical relapse independent of clinicopathologic factors predicting recurrence. CONCLUSION: This study identifies E6AP and PML as potential prognostic markers in localized prostate carcinoma and supports a role for E6AP in driving the downregulation or loss of PML expression in prostate carcinomas.

Type Journal
ISBN 1569-8041 (Electronic) 0923-7534 (Linking)
Authors Birch, S. E. ; Kench, J. G. ; Takano, E. ; Chan, P. ; Chan, A. L. ; Chiam, K. ; Veillard, A. S. ; Stricker, P. ; Haupt, S. ; Haupt, Y. ; Horvath, L. ; Fox, S. B.;
Publisher Name Annals Of Oncology
Published Date 2014-09-01
Published Volume 25
Published Issue 12
Published Pages 2392-7
Status Published in-print
URL link to publisher's version
OpenAccess link to author's accepted manuscript version