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

SE Birch, JG Kench, E Takano, P Chan, AL Chan, Karen Chiam, AS Veillard, P Stricker, S Haupt, Y Haupt, Lisa Horvath, SB Fox

    Research output: Contribution to journalArticlepeer-review

    14 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)2392-2397
    Number of pages6
    JournalAnnals of Oncology
    Volume25
    Issue number12
    DOIs
    Publication statusPublished - 1 Dec 2014

    Keywords

    • Cancer recurrence
    • E6AP
    • PML
    • Prognostic marker
    • Prostate cancer

    Fingerprint Dive into the research topics of 'Expression of E6AP and PML predicts for prostate cancer progression and cancer specific death.'. Together they form a unique fingerprint.

    Cite this