Wolfson Institute of Preventive Medicine - Barts and The London

Molecular markers for prognosis of prostate cancer

Centre for Cancer Prevention

Project Investigator:  Professor Jack Cuzick

Overview

For more than a decade we have been assembling a cohort of men with clinically localised prostate cancer who have been managed conservatively.

We have collected diagnostic tumour blocks as well as clinical information on PSA, clinical stage, and all samples have had Gleason grade read using a contemporary interpretation.  Many important markers have been identified. By far the most predictive has been a 31 gene expression profile based on cell cycle genes.

Current work continues to validate this score, especially in needle biopsies, and to explore new genes and the value of DNA methylation of selected genes.

Other work will examine heterogeneity in the scoreacross the full tumour and the value of this score in serial biopsies in providing early indicators of progression.

Publications

Prognostic value of PTEN loss in men with conservatively managed localised prostate cancer. Br J Cancer. 2013 Jun 25;108(12):2582-9.
Cuzick J, Yang ZH, Fisher G, Tikishvili E, Stone S, Lanchbury JS, Camacho N, Merson S, Brewer D, Cooper CS, Clark J, Berney DM, Møller H, Scardino P, Sangale Z.

Prognostic value of Ki-67 for prostate cancer death in a conservatively managed cohort. Br J Cancer. 2013 Feb 5;108(2):271-7.
Fisher G, Yang ZH, Kudahetti S, Møller H, Scardino P, Cuzick J, Berney DM.

Association between DNA methylation of HSPB1 and death in low Gleason score prostate cancer. Prostate Cancer Prostatic Dis. 2013 Mar;16(1):35-40.
Vasiljević N, Ahmad AS, Beesley C, Thorat MA, Fisher G, Berney DM, Møller H, Yu Y, Lu YJ, Cuzick J, Foster CS, Lorincz AT.

Effects of cyclin D1 gene amplification and protein expression on time to recurrence in postmenopausal breast cancer patients treated with anastrozole or tamoxifen: A TransATAC study. Breast Cancer Res. 2012 Apr 4;14(2):R57.
Lundgren K, Brown M, Pineda S, Cuzick J, Salter J, Zabaglo L, Howell A, Dowsett M, Landberg G, TransATAC Investigators.

Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. Br J Cancer. 2012 Mar 13;106(6):1095-9.
Cuzick J, Berney DM, Fisher G, Mesher D, Møller H, Reid JE, Perry M, Park J, Younus A, Gutin A, Fosher CS, Scardino P, Lanchbury JS, Stone S; Transatlantic Prostate Group.

Absolute quantitation of DNA methylation of 28 candidate genes in prostate cancer using pyrosequencing. Dis Markers. 2011 Jan 1;30(4):151-61.
Vasiljević N, Wu K, Brentnall AR, Kim DC, Thorat MA, Kudahetti SC, Mao X, Xue L, Yu Y, Shaw GL, Beltran L, Lu YJ, Berney DM, Cuzick J, Lorincz AT.

Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study. Lancet Onc. 2011 Mar;12(3):245-255.
Cuzick J, Swanson G, Fisher G, Brothman A, Berney D, Reid J, Mesher D, Speights V, Stankiewicz E, Foster C, Møller H, Scardino P, Warren J, Park J, Younus A, Flake D, Wagner S, Gutin A, Lanchbury J, Stone S; Transatlantic Prostate Group.

Immunohistochemistry for p16, but not Rb or p21, is an independent predictor of prognosis in conservatively treated, clinically localised prostate cancer. Pathology. 2010;42(6):519-23.
Kudahetti SC, Fisher G, Ambroisine L, Prowse D, Kattan MW, Foster CS, Møller H, Oliver T, Fletcher A, Cooper C, Reuter V, Scardino P, Cuzick J, Berney DM; Transatlantic Prostate Group.

Evaluation of prediagnostic prostate-specific antigen dynamics as predictors of death from prostate cancer in patients treated conservatively. Int J Cancer. 2010 Jul 23. 128(10):2373-81.
O'Brien FM, Cronin AM, Fearn PA, Savage CJ, Smith B, Stasi J, Scardino PT, Fisher G, Cuzick J, Møller H, Oliver RT, Berney DM, Foster CS, Eastham JA, Vickers AJ, Lilja H; Transatlantic Prostate Group.

Molecular characterisation of ERG, ETV1 and PTEN gene loci identifies patients at low and high risk of death from prostate cancer. Br J Cancer, 2010 Feb:16;102(4):678-84.
Reid AH, Attard G, Ambroisine L, Fisher G, Kovacs G, Brewer D, Clark J, Flohr P, Edwards S, Berney DM, Foster CS, Fletcher A, Gerald WL, Møller H, Reuter VE, Scardino PT, Cuzick J, de Bono JS, Cooper CS; Transatlantic Prostate Group.

SOX9 elevation in the prostate promotes proliferation and cooperates with PTEN loss to drive tumor formation. Cancer Res. 2010 Feb 1;70(3):979-87.
Thomsen MK, Ambroisine L, Wynn S, Cheah KS, Foster CS, Fisher G, Berney DM, Møller H, Reuter VE, Scardino P, Cuzick J, Ragavan N, Singh PB, Martin FL, Butler CM, Cooper CS, Swain A, Transatlantic Prostate Group.

Ki-67 and outcome in clinically localised prostate cancer: analysis of conservatively treated prostate cancer patients from the Trans-Atlantic Prostate Group study. Br J Cancer. 2009 Mar 24;100(6):888-93.
Berney DM, Gopalan A, Kudahetti S, Fisher G, Ambroisine L, Foster CS, Reuter V, Eastham J, Moller H, Kattan MW, Gerald W, Cooper C, Scardino P, Cuzick J.

Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer. Br J Cancer. 2008 Jul 22;99(2):314-20.
Attard G, Clark J, Ambroisine L, Mills IG, Fisher G, Flohr P, Reid A, Edwards S, Kovacs G, Berney D, Foster C, Massie CE, Fletcher A, De Bono JS, Scardino P, Cuzick J, Cooper CS; Transatlantic Prostate Group.

Major shifts in the treatment and prognosis of prostate cancer due to changes in pathological diagnosis and grading. BJU Int. 2007 Dec;100(6):1240-4.
Berney DM, Fisher G, Kattan MW, Oliver RT, Møller H, Fearn P, Eastham J, Scardino P, Cuzick J, Reuter VE, Foster CS; Trans-Atlantic Prostate Group.

Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer. Oncogene. 2008 Jan 10;27(3):253-63.
Attard G, Clark J, Ambroisine L, Fisher G, Kovacs G, Flohr P, Berney D, Foster CS, Fletcher A, Gerald WL, Moller H, Reuter V, De Bono JS, Scardino P, Cuzick J, Cooper CS.

Long-term outcome among men with conservatively treated localised prostate cancer. Br J Cancer. 2006 Nov 6; 95(9): 1186-94.
Cuzick J, Fisher G, Kattan MW, Berney D, Oliver T, Foster CS, Moller H, Reuter V, Fearn P, Eastham J, Scardino P.