Anuradha Gopalan1, Tamara L Lotan2,3,4, Nora M Haney2, Farzana A Faisal2, Jiayun Lu5, Liana B Guedes3, Victor E Reuter1, Howard I Scher6, James A Eastham7, Luigi Marchionni4,8, Corinne Joshu5. 1. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. 2. Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland. 3. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. 4. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. 5. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland. 6. Department of Genitourinary Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. 7. Department of Urology, Memorial Sloan Kettering Cancer Center, New York, New York. 8. Center for Computational Genomics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Abstract
PURPOSE: Few groups have investigated the combined effects of PTEN loss and ERG expression on the outcomes of metastasis of or death from prostate cancer in surgically treated patients. We examined the association of PTEN/ERG status with lethal prostate cancer in patients treated with radical prostatectomy. MATERIALS AND METHODS: Included in analysis were 791 patients with clinically localized prostate cancer treated with radical prostatectomy at a single institution. Genetically validated immunohistochemistry assays for PTEN and ERG were performed on tissue microarrays. Multivariable Cox proportional hazard models were used to assess the association of PTEN/ERG status with lethal prostate cancer (defined as metastasis or prostate cancer specific death), adjusting for patient age, race, pathological grade and stage, and surgical margin status. RESULTS: Median followup in the cohort was 12.8 years. Of 791 cases 203 (25%) demonstrated PTEN loss and 330 of 776 (43%) were ERG positive. On multivariable analysis PTEN loss (HR 1.9, 95% CI 1.2-3.0, p=0.012) but not ERG expression (HR 0.6, 95% CI 0.4-1.1, p=0.11) was associated with an increased risk of lethal prostate cancer. The association of PTEN loss with lethal disease only remained among men with ERG negative tumors (HR 2.3, 95% CI 1.3-4.1, p=0.005) and not ERG positive tumors (HR 1.1, 95% CI 0.6-2.1, p=0.81). CONCLUSIONS: PTEN loss is associated with an increased risk of lethal prostate cancer after radical prostatectomy and this risk is most pronounced in the subgroup of patients with ERG negative tumors. This work corroborates the use of PTEN and ERG status for risk stratification in surgically treated patients.
PURPOSE: Few groups have investigated the combined effects of PTEN loss and ERG expression on the outcomes of metastasis of or death from prostate cancer in surgically treated patients. We examined the association of PTEN/ERG status with lethal prostate cancer in patients treated with radical prostatectomy. MATERIALS AND METHODS: Included in analysis were 791 patients with clinically localized prostate cancer treated with radical prostatectomy at a single institution. Genetically validated immunohistochemistry assays for PTEN and ERG were performed on tissue microarrays. Multivariable Cox proportional hazard models were used to assess the association of PTEN/ERG status with lethal prostate cancer (defined as metastasis or prostate cancer specific death), adjusting for patient age, race, pathological grade and stage, and surgical margin status. RESULTS: Median followup in the cohort was 12.8 years. Of 791 cases 203 (25%) demonstrated PTEN loss and 330 of 776 (43%) were ERG positive. On multivariable analysis PTEN loss (HR 1.9, 95% CI 1.2-3.0, p=0.012) but not ERG expression (HR 0.6, 95% CI 0.4-1.1, p=0.11) was associated with an increased risk of lethal prostate cancer. The association of PTEN loss with lethal disease only remained among men with ERG negative tumors (HR 2.3, 95% CI 1.3-4.1, p=0.005) and not ERG positive tumors (HR 1.1, 95% CI 0.6-2.1, p=0.81). CONCLUSIONS: PTEN loss is associated with an increased risk of lethal prostate cancer after radical prostatectomy and this risk is most pronounced in the subgroup of patients with ERG negative tumors. This work corroborates the use of PTEN and ERG status for risk stratification in surgically treated patients.
Authors: Janielle P Maynard; Jiayun Lu; Igor Vidal; Jessica Hicks; Luke Mummert; Tamirat Ali; Ryan Kempski; Ayanna M Carter; Rebecca Y Sosa; Lauren B Peiffer; Corinne E Joshu; Tamara L Lotan; Angelo M De Marzo; Karen S Sfanos Journal: J Pathol Date: 2021-11-25 Impact factor: 7.996
Authors: Adam B Weiner; Thiago Vidotto; Yang Liu; Adrianna A Mendes; Daniela C Salles; Farzana A Faisal; Sanjana Murali; Matthew McFarlane; Eddie L Imada; Xin Zhao; Ziwen Li; Elai Davicioni; Luigi Marchionni; Arul M Chinnaiyan; Stephen J Freedland; Daniel E Spratt; Jennifer D Wu; Tamara L Lotan; Edward M Schaeffer Journal: Nat Commun Date: 2021-02-10 Impact factor: 17.694
Authors: Christopher M Heaphy; Corinne E Joshu; Elizabeth A Platz; Alan K Meeker; John R Barber; Christine Davis; Jiayun Lu; Reza Zarinshenas; Edward Giovannucci; Lorelei A Mucci; Meir J Stampfer; Misop Han; Angelo M De Marzo; Tamara L Lotan Journal: J Pathol Clin Res Date: 2022-07-14