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.
Medical oncology (Northwood, London, England). 2018 Oct 05*** epublish ***
Rohit Mehra, Simpa S Salami, Robert Lonigro, Ritu Bhalla, Javed Siddiqui, Xuhong Cao, Daniel E Spratt, Ganesh S Palapattu, Nallasivam Palanisamy, John T Wei, Arul M Chinnaiyan, Scott A Tomlins
Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA. ., University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA., Michigan Center for Translational Pathology, Ann Arbor, MI, USA., LSU Health Sciences Center, New Orleans, MI, USA., Department of Urology, Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, USA., Department of Urology, University of Michigan Health System, Ann Arbor, MI, USA., Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA., Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA. .