Alexandra L Tabakin1, Evita T Sadimin2, Irina Tereshchenko3, Aparna Kareddula3, Mark N Stein3, Tina Mayer3, Kim M Hirshfield3, Isaac Y Kim1, Jay Tischfield4, Robert S DiPaola3, Eric A Singer1. 1. Division of Urologic Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, USA. 2. Section of Pathologic Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, USA. 3. Division of Medical Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, USA. 4. Department of Genetics, Human Genetics Institute of New Jersey and Rutgers University, USA.
Abstract
INTRODUCTION: CHD1 has been identified as a tumor suppressor gene in prostate cancer. Previous studies have shown strong associations between CHD1 deletion, prostate specific antigen [PSA] recurrence, and absence of ERG fusion. In this preliminary study we seek to find whether there is an independent correlation between CHD1 status and response to androgen deprivation therapy[ADT]. MATERIALS AND METHODS: We identified 11 patients with prostate cancer who underwent prostatectomy and received at least 7 months of ADT at our institution. They were divided into undetectable [PSA < 0.2 ng/mL; n = 8] and detectable [PSA > 0.2 ng/mL; n = 3] according to their serum PSA nadir after 7 months of ADT. Tissue microarray was generated from their formalin-fixed paraffin-embedded prostatectomy and involved lymph node tissues. Fluorescence in situ hybridization [FISH] analysis for CHD1 and immunohistochemical stains for PSA, AR, PTEN, ERG and SPINK1 were performed. RESULTS: Our results showed heterogeneity of FISH and immunostains expressions in different foci of tumor. Status of CHD1, ERG, PTEN, or SPINK1 did not correlate with one another or with response to ADT. CONCLUSIONS: Additional larger studies may be needed to further elucidate trends between these biomarkers and clinical outcomes in prostate cancer patients.
INTRODUCTION: CHD1 has been identified as a tumor suppressor gene in prostate cancer. Previous studies have shown strong associations between CHD1 deletion, prostate specific antigen [PSA] recurrence, and absence of ERG fusion. In this preliminary study we seek to find whether there is an independent correlation between CHD1 status and response to androgen deprivation therapy[ADT]. MATERIALS AND METHODS: We identified 11 patients with prostate cancer who underwent prostatectomy and received at least 7 months of ADT at our institution. They were divided into undetectable [PSA < 0.2 ng/mL; n = 8] and detectable [PSA > 0.2 ng/mL; n = 3] according to their serum PSA nadir after 7 months of ADT. Tissue microarray was generated from their formalin-fixed paraffin-embedded prostatectomy and involved lymph node tissues. Fluorescence in situ hybridization [FISH] analysis for CHD1 and immunohistochemical stains for PSA, AR, PTEN, ERG and SPINK1 were performed. RESULTS: Our results showed heterogeneity of FISH and immunostains expressions in different foci of tumor. Status of CHD1, ERG, PTEN, or SPINK1 did not correlate with one another or with response to ADT. CONCLUSIONS: Additional larger studies may be needed to further elucidate trends between these biomarkers and clinical outcomes in prostate cancer patients.
Entities:
Keywords:
Androgen deprivation therapy; CHD1; Genetics; Prostate cancer
Authors: Michael S Cookson; Gunnar Aus; Arthur L Burnett; Edith D Canby-Hagino; Anthony V D'Amico; Roger R Dmochowski; David T Eton; Jeffrey D Forman; S Larry Goldenberg; Javier Hernandez; Celestia S Higano; Stephen R Kraus; Judd W Moul; Catherine Tangen; J Brantley Thrasher; Ian Thompson Journal: J Urol Date: 2007-02 Impact factor: 7.450
Authors: H Ballentine Carter; Alan W Partin; Patrick C Walsh; Bruce J Trock; Robert W Veltri; William G Nelson; Donald S Coffey; Eric A Singer; Jonathan I Epstein Journal: J Clin Oncol Date: 2012-10-01 Impact factor: 44.544
Authors: Andreas Pettersson; Rebecca E Graff; Scott R Bauer; Michael J Pitt; Rosina T Lis; Edward C Stack; Neil E Martin; Lauren Kunz; Kathryn L Penney; Azra H Ligon; Catherine Suppan; Richard Flavin; Howard D Sesso; Jennifer R Rider; Christopher Sweeney; Meir J Stampfer; Michelangelo Fiorentino; Philip W Kantoff; Martin G Sanda; Edward L Giovannucci; Eric L Ding; Massimo Loda; Lorelei A Mucci Journal: Cancer Epidemiol Biomarkers Prev Date: 2012-06-26 Impact factor: 4.254
Authors: Sarah Minner; Malaika Enodien; Hüseyin Sirma; Andreas M Luebke; Antje Krohn; Pascale S Mayer; Ronald Simon; Pierre Tennstedt; Julia Müller; Laura Scholz; Jan C Brase; Alvin Y Liu; Hartmut Schlüter; Klaus Pantel; Udo Schumacher; Carsten Bokemeyer; Thomas Steuber; Markus Graefen; Guido Sauter; Thorsten Schlomm Journal: Clin Cancer Res Date: 2011-07-26 Impact factor: 12.531
Authors: Maha Hussain; Catherine M Tangen; Celestia Higano; Paul F Schelhammer; James Faulkner; E David Crawford; George Wilding; Atif Akdas; Eric J Small; Bryan Donnelly; Gary MacVicar; Derek Raghavan Journal: J Clin Oncol Date: 2006-08-20 Impact factor: 44.544
Authors: Rohit Mehra; Scott A Tomlins; Ronglai Shen; Owais Nadeem; Lei Wang; John T Wei; Kenneth J Pienta; Debashis Ghosh; Mark A Rubin; Arul M Chinnaiyan; Rajal B Shah Journal: Mod Pathol Date: 2007-03-02 Impact factor: 7.842
Authors: J Clark; G Attard; S Jhavar; P Flohr; A Reid; J De-Bono; R Eeles; P Scardino; J Cuzick; G Fisher; M D Parker; C S Foster; D Berney; G Kovacs; C S Cooper Journal: Oncogene Date: 2007-10-08 Impact factor: 9.867
Authors: Scott A Tomlins; Anders Bjartell; Arul M Chinnaiyan; Guido Jenster; Robert K Nam; Mark A Rubin; Jack A Schalken Journal: Eur Urol Date: 2009-04-24 Impact factor: 20.096
Authors: Catherine S Grasso; Yi-Mi Wu; Dan R Robinson; Xuhong Cao; Saravana M Dhanasekaran; Amjad P Khan; Michael J Quist; Xiaojun Jing; Robert J Lonigro; J Chad Brenner; Irfan A Asangani; Bushra Ateeq; Sang Y Chun; Javed Siddiqui; Lee Sam; Matt Anstett; Rohit Mehra; John R Prensner; Nallasivam Palanisamy; Gregory A Ryslik; Fabio Vandin; Benjamin J Raphael; Lakshmi P Kunju; Daniel R Rhodes; Kenneth J Pienta; Arul M Chinnaiyan; Scott A Tomlins Journal: Nature Date: 2012-07-12 Impact factor: 49.962
Authors: Aparna Kareddula; Daniel J Medina; Whitney Petrosky; Sonia Dolfi; Irina Tereshchenko; Kelly Walton; Hana Aviv; Evita Sadimin; Alexandra L Tabakin; Eric A Singer; Kim M Hirshfield Journal: Ther Adv Urol Date: 2021-08-04