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Association of ERG/PTEN status with biochemical recurrence after radical prostatectomy for clinically localized prostate cancer

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Abstract

We have previously demonstrated a significant correlative relationship between PTEN deletion and ERG rearrangement, both in the development of clinically localized prostate cancers and metastases. Herein, we evaluate the cooperative role of ERG and PTEN in oncological outcomes after radical prostatectomy for clinically localized prostate cancer. We evaluated ERG and PTEN status using three previously described cohorts. The first cohort included 235 clinically localized prostate cancer cases represented on tissue microarrays (TMA), evaluated using previously validated FISH assays for ERG and PTEN. The second cohort included 167 cases of clinically localized prostate cancer on TMAs evaluated for PTEN by FISH, and for PTEN and ERG by dual IHC. The third cohort comprised 59 clinically localized prostate cancer cases assessed by array comparative genomic hybridization (aCGH). Kaplan–Meir plots and long rank tests were used to assess the association of ERG and PTEN status with biochemical recurrence after radical prostatectomy for clinically localized prostate cancer. Of the 317 cases eligible for analyses with evaluable ERG and PTEN status, 88 (27.8%) patients developed biochemical recurrence over a median follow-up of 5.7 years. Overall, 45% (142/317) of cases demonstrated ERG rearrangement and 20% (62/317) of cases demonstrated PTEN loss. Hemizygous and homozygous deletion of PTEN was seen in 10% (18/175) and 3% (5/175) of ERG-negative cases, respectively. In contrast, hemizygous and homozygous deletion of PTEN was seen in 11% (15/142) and 17% (24/123) of ERG-positive cases, respectively. PTEN loss (heterozygous or homozygous) was significantly associated with shorter time to biochemical recurrence compared to no PTEN loss (p < 0.001). However, ERG rearrangement versus no rearrangement was not associated with time to PSA recurrence (p = 0.15). Patients who exhibited ERG rearrangement and loss of PTEN had no significant difference in time to recurrence compared to patients with wild-type ERG and loss of PTEN (p = 0.30). Our findings confirm a mutual cooperative role of ERG and PTEN in the pathogenesis of prostate cancer, particularly for homozygous PTEN deletion. ERG did not stratify outcome either alone or in combination with PTEN in this cohort.

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Funding

S.S.S. is supported by the Urology Care Foundation and the Prostate Cancer Foundation. S.A.T. is supported by the A. Alfred Taubman Medical Institute and the Prostate Cancer Foundation. Supported in part by the National Institutes of Health U01 CA214170 to A.M.C. and the University of Michigan Prostate Specialized Program of Research Excellence [S.P.O.R.E.] P50 CA186786-05. D.E.S. has been supported by the Department of Defense.

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Authors and Affiliations

  1. Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA

    Rohit Mehra, Arul M. Chinnaiyan & Scott A. Tomlins

  2. Michigan Center for Translational Pathology, Ann Arbor, MI, USA

    Rohit Mehra, Robert Lonigro, Javed Siddiqui, Xuhong Cao, Arul M. Chinnaiyan & Scott A. Tomlins

  3. University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA

    Rohit Mehra, Simpa S. Salami, Daniel E. Spratt, Ganesh S. Palapattu & Arul M. Chinnaiyan

  4. 2G332 UH, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA

    Rohit Mehra

  5. Department of Urology, University of Michigan Health System, Ann Arbor, MI, USA

    Simpa S. Salami, Ganesh S. Palapattu, John T. Wei & Arul M. Chinnaiyan

  6. LSU Health Sciences Center, New Orleans, MI, USA

    Ritu Bhalla

  7. Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, MI, USA

    Daniel E. Spratt

  8. Department of Urology, Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, USA

    Nallasivam Palanisamy

  9. Howard Hughes Medical Institute, Ann Arbor, MI, USA

    Arul M. Chinnaiyan

  10. 1500 E. Medical Center Dr.,7322 Cancer Center, SPC 5948, Ann Arbor, MI, 48109-5948, USA

    Scott A. Tomlins

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  1. Rohit Mehra
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Correspondence to Rohit Mehra or Scott A. Tomlins.

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Conflict of interest

The University of Michigan has been issued a patent on the detection of ETS gene fusions in prostate cancer, in which R.M., S.A.T., and A.M.C. are listed as co-inventors. The University of Michigan has licensed the diagnostic field of use to Gen-Probe, Inc. (Bedford, MA), which has sublicensed some rights to Ventana Medical Systems. S.A.T. serves as a consultant to and has received honoraria from Ventana Medical Systems. A.M.C. has served as a consultant for Gen-Probe, Inc. and Ventana Medical Systems. All other authors have no disclosures.

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Mehra, R., Salami, S.S., Lonigro, R. et al. Association of ERG/PTEN status with biochemical recurrence after radical prostatectomy for clinically localized prostate cancer. Med Oncol 35, 152 (2018). https://doi.org/10.1007/s12032-018-1212-6

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