Tamara L Lotan1, Wei Wei2, Carlos L Morais3, Sarah T Hawley4, Ladan Fazli5, Antonio Hurtado-Coll5, Dean Troyer6, Jesse K McKenney7, Jeffrey Simko8, Peter R Carroll9, Martin Gleave5, Raymond Lance10, Daniel W Lin11, Peter S Nelson12, Ian M Thompson13, Lawrence D True14, Ziding Feng2, James D Brooks15. 1. Pathology Department, Johns Hopkins School of Medicine, Baltimore, MD, USA; Oncology Department, Johns Hopkins School of Medicine, Baltimore, MD, USA. 2. MD Anderson Cancer Center, Houston, TX, USA. 3. Pathology Department, Johns Hopkins School of Medicine, Baltimore, MD, USA. 4. Canary Foundation, Palo Alto, CA, USA. 5. Vancouver Prostate Centre, Vancouver, BC, Canada. 6. Pathology Department, Eastern Virginia Medical School, Norfolk, VA, USA; Urology Department, Eastern Virginia Medical School, Norfolk, VA, USA. 7. Pathology Department, Cleveland Clinic, Cleveland, OH, USA. 8. Pathology Department, University of California-San Francisco, San Francisco, CA, USA; Urology Department, University of California-San Francisco, San Francisco, CA, USA. 9. Urology Department, University of California-San Francisco, San Francisco, CA, USA. 10. Urology Department, Eastern Virginia Medical School, Norfolk, VA, USA. 11. Urology Department, University of Washington, Seattle, WA, USA. 12. Oncology Department, University of Washington, Seattle, WA, USA; Pathology Department, University of Washington, Seattle, WA, USA. 13. Urology Department, University of Texas Health Science Center, San Antonio, TX, USA. 14. Pathology Department, University of California-San Francisco, San Francisco, CA, USA. 15. Urology Department, Stanford University School of Medicine, Stanford, CA, USA.
Abstract
BACKGROUND: PTEN is the most commonly deleted tumor suppressor gene in primary prostate cancer (PCa) and its loss is associated with poor clinical outcomes and ERG gene rearrangement. OBJECTIVE: We tested whether PTEN loss is associated with shorter recurrence-free survival (RFS) in surgically treated PCa patients with known ERG status. DESIGN SETTING AND PARTICIPANTS: A genetically validated, automated PTEN immunohistochemistry (IHC) protocol was used for 1275 primary prostate tumors from the Canary Foundation retrospective PCa tissue microarray cohort to assess homogeneous (in all tumor tissue sampled) or heterogeneous (in a subset of tumor tissue sampled) PTEN loss. ERG status as determined by a genetically validated IHC assay was available for a subset of 938 tumors. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations between PTEN and ERG status were assessed using Fisher's exact test. Kaplan-Meier and multivariate weighted Cox proportional models for RFS were constructed. RESULTS AND LIMITATIONS: When compared to intact PTEN, homogeneous (hazard ratio [HR] 1.66, p = 0.001) but not heterogeneous (HR 1.24, p = 0.14) PTEN loss was significantly associated with shorter RFS in multivariate models. Among ERG-positive tumors, homogeneous (HR 3.07, p < 0.0001) but not heterogeneous (HR 1.46, p = 0.10) PTEN loss was significantly associated with shorter RFS. Among ERG-negative tumors, PTEN did not reach significance for inclusion in the final multivariate models. The interaction term for PTEN and ERG status with respect to RFS did not reach statistical significance (p = 0.11) for the current sample size. CONCLUSIONS: These data suggest that PTEN is a useful prognostic biomarker and that there is no statistically significant interaction between PTEN and ERG status for RFS. PATIENT SUMMARY: We found that loss of the PTEN tumor suppressor gene in prostate tumors as assessed by tissue staining is correlated with shorter time to prostate cancer recurrence after radical prostatectomy.
BACKGROUND:PTEN is the most commonly deleted tumor suppressor gene in primary prostate cancer (PCa) and its loss is associated with poor clinical outcomes and ERG gene rearrangement. OBJECTIVE: We tested whether PTEN loss is associated with shorter recurrence-free survival (RFS) in surgically treated PCa patients with known ERG status. DESIGN SETTING AND PARTICIPANTS: A genetically validated, automated PTEN immunohistochemistry (IHC) protocol was used for 1275 primary prostate tumors from the Canary Foundation retrospective PCa tissue microarray cohort to assess homogeneous (in all tumor tissue sampled) or heterogeneous (in a subset of tumor tissue sampled) PTEN loss. ERG status as determined by a genetically validated IHC assay was available for a subset of 938 tumors. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations between PTEN and ERG status were assessed using Fisher's exact test. Kaplan-Meier and multivariate weighted Cox proportional models for RFS were constructed. RESULTS AND LIMITATIONS: When compared to intact PTEN, homogeneous (hazard ratio [HR] 1.66, p = 0.001) but not heterogeneous (HR 1.24, p = 0.14) PTEN loss was significantly associated with shorter RFS in multivariate models. Among ERG-positive tumors, homogeneous (HR 3.07, p < 0.0001) but not heterogeneous (HR 1.46, p = 0.10) PTEN loss was significantly associated with shorter RFS. Among ERG-negative tumors, PTEN did not reach significance for inclusion in the final multivariate models. The interaction term for PTEN and ERG status with respect to RFS did not reach statistical significance (p = 0.11) for the current sample size. CONCLUSIONS: These data suggest that PTEN is a useful prognostic biomarker and that there is no statistically significant interaction between PTEN and ERG status for RFS. PATIENT SUMMARY: We found that loss of the PTEN tumor suppressor gene in prostate tumors as assessed by tissue staining is correlated with shorter time to prostate cancer recurrence after radical prostatectomy.
Authors: Antje Krohn; Tobias Diedler; Lia Burkhardt; Pascale-Sophie Mayer; Colin De Silva; Marie Meyer-Kornblum; Darja Kötschau; Pierre Tennstedt; Joseph Huang; Clarissa Gerhäuser; Malte Mader; Stefan Kurtz; Hüseyin Sirma; Fred Saad; Thomas Steuber; Markus Graefen; Christoph Plass; Guido Sauter; Ronald Simon; Sarah Minner; Thorsten Schlomm Journal: Am J Pathol Date: 2012-06-13 Impact factor: 4.307
Authors: Matthew R Cooperberg; Elai Davicioni; Anamaria Crisan; Robert B Jenkins; Mercedeh Ghadessi; R Jeffrey Karnes Journal: Eur Urol Date: 2014-07-02 Impact factor: 20.096
Authors: Kanishka Sircar; Maisa Yoshimoto; Federico A Monzon; Ismael H Koumakpayi; Ruth L Katz; Abha Khanna; Karla Alvarez; Guanyong Chen; Andrew D Darnel; Armen G Aprikian; Fred Saad; Tarek A Bismar; Jeremy A Squire Journal: J Pathol Date: 2009-08 Impact factor: 7.996
Authors: Brett S Carver; Jennifer Tran; Anuradha Gopalan; Zhenbang Chen; Safa Shaikh; Arkaitz Carracedo; Andrea Alimonti; Caterina Nardella; Shohreh Varmeh; Peter T Scardino; Carlos Cordon-Cardo; William Gerald; Pier Paolo Pandolfi Journal: Nat Genet Date: 2009-04-26 Impact factor: 38.330
Authors: Maisa Yoshimoto; Anthony M Joshua; Isabela W Cunha; Renata A Coudry; Francisco P Fonseca; Olga Ludkovski; Maria Zielenska; Fernando A Soares; Jeremy A Squire Journal: Mod Pathol Date: 2008-05-23 Impact factor: 7.842
Authors: Michael F Berger; Michael S Lawrence; Francesca Demichelis; Yotam Drier; Kristian Cibulskis; Andrey Y Sivachenko; Andrea Sboner; Raquel Esgueva; Dorothee Pflueger; Carrie Sougnez; Robert Onofrio; Scott L Carter; Kyung Park; Lukas Habegger; Lauren Ambrogio; Timothy Fennell; Melissa Parkin; Gordon Saksena; Douglas Voet; Alex H Ramos; Trevor J Pugh; Jane Wilkinson; Sheila Fisher; Wendy Winckler; Scott Mahan; Kristin Ardlie; Jennifer Baldwin; Jonathan W Simons; Naoki Kitabayashi; Theresa Y MacDonald; Philip W Kantoff; Lynda Chin; Stacey B Gabriel; Mark B Gerstein; Todd R Golub; Matthew Meyerson; Ashutosh Tewari; Eric S Lander; Gad Getz; Mark A Rubin; Levi A Garraway Journal: Nature Date: 2011-02-10 Impact factor: 49.962
Authors: B Gumuskaya; B Gurel; H Fedor; H-L Tan; C A Weier; J L Hicks; M C Haffner; T L Lotan; A M De Marzo Journal: Prostate Cancer Prostatic Dis Date: 2013-04-02 Impact factor: 5.554
Authors: A H M Reid; G Attard; L Ambroisine; G Fisher; G Kovacs; D Brewer; J Clark; P Flohr; S Edwards; D M Berney; C S Foster; A Fletcher; W L Gerald; H Møller; V E Reuter; P T Scardino; J Cuzick; J S de Bono; C S Cooper Journal: Br J Cancer Date: 2010-01-26 Impact factor: 7.640
Authors: J Cuzick; Z H Yang; G Fisher; E Tikishvili; S Stone; J S Lanchbury; N Camacho; S Merson; D Brewer; C S Cooper; J Clark; D M Berney; H Møller; P Scardino; Z Sangale Journal: Br J Cancer Date: 2013-05-21 Impact factor: 7.640
Authors: M Yoshimoto; I W Cunha; R A Coudry; F P Fonseca; C H Torres; F A Soares; J A Squire Journal: Br J Cancer Date: 2007-08-14 Impact factor: 7.640
Authors: James D Brooks; Wei Wei; Jonathan R Pollack; Robert B West; Jun Ho Shin; John B Sunwoo; Sarah J Hawley; Heidi Auman; Lisa F Newcomb; Jeff Simko; Antonio Hurtado-Coll; Dean A Troyer; Peter R Carroll; Martin E Gleave; Daniel W Lin; Peter S Nelson; Ian M Thompson; Lawrence D True; Jesse K McKenney; Ziding Feng; Ladan Fazli Journal: Prostate Date: 2016-06-21 Impact factor: 4.104
Authors: Michael C Haffner; Wilbert Zwart; Martine P Roudier; Lawrence D True; William G Nelson; Jonathan I Epstein; Angelo M De Marzo; Peter S Nelson; Srinivasan Yegnasubramanian Journal: Nat Rev Urol Date: 2020-12-16 Impact factor: 14.432
Authors: Tamara Jamaspishvili; David M Berman; Ashley E Ross; Howard I Scher; Angelo M De Marzo; Jeremy A Squire; Tamara L Lotan Journal: Nat Rev Urol Date: 2018-02-20 Impact factor: 14.432
Authors: Daniel E Spratt; Mohammed Alshalalfa; Nick Fishbane; Adam B Weiner; Rohit Mehra; Brandon A Mahal; Jonathan Lehrer; Yang Liu; Shuang G Zhao; Corey Speers; Todd M Morgan; Adam P Dicker; Stephen J Freedland; R Jeffery Karnes; Sheila Weinmann; Elai Davicioni; Ashley E Ross; Robert B Den; Paul L Nguyen; Felix Y Feng; Tamara L Lotan; Arul M Chinnaiyan; Edward M Schaeffer Journal: Clin Cancer Res Date: 2019-09-12 Impact factor: 12.531
Authors: Liana B Guedes; Emmanuel S Antonarakis; Michael T Schweizer; Nooshin Mirkheshti; Fawaz Almutairi; Jong Chul Park; Stephanie Glavaris; Jessica Hicks; Mario A Eisenberger; Angelo M De Marzo; Jonathan I Epstein; William B Isaacs; James R Eshleman; Colin C Pritchard; Tamara L Lotan Journal: Clin Cancer Res Date: 2017-08-08 Impact factor: 12.531
Authors: Erin Baumgartner; Maria Del Carmen Rodriguez Pena; Marie-Lisa Eich; Kristin K Porter; Jeffrey W Nix; Soroush Rais-Bahrami; Jennifer Gordetsky Journal: Hum Pathol Date: 2019-05-07 Impact factor: 3.466