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The role of treatment modality on the utility of predictive tissue biomarkers in clinical prostate cancer: a systematic review

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Abstract

Background

Tissue biomarkers could pivotally improve clinical outcome prediction following prostate cancer therapy. Clinically, prostate cancer is managed by diverse treatment modalities whose individual influence on a biomarker’s predictive ability is not well understood and poorly investigated in the literature.

Objective

We conducted a systematic review to assess the predictive value of biomarkers in different treatment contexts in prostate cancer.

Study methodology

A literature search was performed using the MeSH headings “prostate neoplasms” and “biological markers”. Rigorous selection criteria identified studies correlating expression with clinical outcomes from primary androgen deprivation therapy (ADT), radical prostatectomy and radiotherapy (± neoadjuvant ADT).

Study results

Of 10,668 studies identified, 481 papers matched initial inclusion criteria. Following rescreening, 384 studies identified 236 individual tissue biomarkers, of which 29 were predictive on multivariate analysis in at least 2 independent cohorts. The majority were only tested in surgical cohorts. Only 8 predictive biomarkers were tested across all 3 treatments with Ki67 identified as universal predictive marker. p16 showed potential for treatment stratification between surgery and radiotherapy but needs further validation in independent studies.

Conclusions

Despite years of research, very few tissue biomarkers retain predictive value in independent validation across therapy context. Currently, none have conclusive ability to help treatment selection. Future biomarker research should consider the therapy context and use uniform methodology and evaluation criteria.

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References

  • Aaltomaa S, Lipponen P, Viitanen J, Kankkunen JP, Ala-Opas M, Kosma VM (2000) Prognostic value of CD44 standard, variant isoforms 3 and 6 and -catenin expression in local prostate cancer treated by radical prostatectomy. Eur Urol 38(5):555–562

    Article  PubMed  CAS  Google Scholar 

  • American College of Surgeons (2012) National Cancer Database Public Reports 2000–2009. http://www.facs.org/cancer/ncdb

  • Amling CL, Lerner SE, Martin SK, Slezak JM, Blute ML, Zincke H (1999) Deoxyribonucleic acid ploidy and serum prostate specific antigen predict outcome following salvage prostatectomy for radiation refractory prostate cancer. J Urol 161(3):857–862; discussion 853–862

    Google Scholar 

  • Ayala G, Thompson T, Yang G, Frolov A, Li R, Scardino P, Ohori M, Wheeler T, Harper W (2004) High levels of phosphorylated form of Akt-1 in prostate cancer and non-neoplastic prostate tissues are strong predictors of biochemical recurrence. Clin Cancer Res 10(19):6572–6578

    Article  PubMed  CAS  Google Scholar 

  • Baretton GB, Klenk U, Diebold J, Schmeller N, Lohrs U (1999) Proliferation- and apoptosis-associated factors in advanced prostatic carcinomas before and after androgen deprivation therapy: prognostic significance of p21/WAF1/CIP1 expression. Br J Cancer 80(3–4):546–555

    Article  PubMed  CAS  Google Scholar 

  • Barwick BG, Abramovitz M, Kodani M, Moreno CS, Nam R, Tang W, Bouzyk M, Seth A, Leyland-Jones B (2010) Prostate cancer genes associated with TMPRSS2-ERG gene fusion and prognostic of biochemical recurrence in multiple cohorts. Br J Cancer 102(3):570–576

    Article  PubMed  CAS  Google Scholar 

  • Bedolla R, Prihoda TJ, Kreisberg JI, Malik SN, Krishnegowda NK, Troyer DA, Ghosh PM (2007) Determining risk of biochemical recurrence in prostate cancer by immunohistochemical detection of PTEN expression and Akt activation. Clin Cancer Res 13(13):3860–3867

    Article  PubMed  CAS  Google Scholar 

  • Berglund RK, Jones JS, Ulchaker JC, Fergany A, Gill I, Kaouk J, Klein EA (2006) Radical prostatectomy as primary treatment modality for locally advanced prostate cancer: a prospective analysis. Urology 67(6):1253–1256

    Article  PubMed  Google Scholar 

  • 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 (2009) 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 100(6):888–893

    Article  PubMed  CAS  Google Scholar 

  • Berruti A, Mosca A, Porpiglia F, Bollito E, Tucci M, Vana F, Cracco C, Torta M, Russo L, Cappia S, Saini A, Angeli A, Papotti M, Scarpa RM, Dogliotti L (2007) Chromogranin A expression in patients with hormone naive prostate cancer predicts the development of hormone refractory disease. J Urol 178 (3 Pt 1):838–843: quiz 1129

    Google Scholar 

  • Berruti A, Bollito E, Cracco CM, Volante M, Ciccone G, Porpiglia F, Papotti M, Scarpa RM, Dogliotti L (2010) The prognostic role of immunohistochemical chromogranin a expression in prostate cancer patients is significantly modified by androgen-deprivation therapy. Prostate 70(7):718–726

    PubMed  Google Scholar 

  • Bjartell AS, Al-Ahmadie H, Serio AM, Eastham JA, Eggener SE, Fine SW, Udby L, Gerald WL, Vickers AJ, Lilja H, Reuter VE, Scardino PT (2007) Association of cysteine-rich secretory protein 3 and beta-microseminoprotein with outcome after radical prostatectomy. Clin Cancer Res 13(14):4130–4138

    Article  PubMed  CAS  Google Scholar 

  • Blute ML, Bergstralh EJ, Iocca A, Scherer B, Zincke H (2001) Use of Gleason score, prostate specific antigen, seminal vesicle and margin status to predict biochemical failure after radical prostatectomy. J Urol 165(1):119–125

    Article  PubMed  CAS  Google Scholar 

  • Bracarda S, Logothetis C, Sternberg CN, Oudard S (2011) Current and emerging treatment modalities for metastatic castration-resistant prostate cancer. BJU Int 107(Suppl 2):13–20

    Article  PubMed  CAS  Google Scholar 

  • Brewster SF, Oxley JD, Trivella M, Abbott CD, Gillatt DA (1999) Preoperative p53, bcl-2, CD44 and E-cadherin immunohistochemistry as predictors of biochemical relapse after radical prostatectomy. J Urol 161(4):1238–1243

    Article  PubMed  CAS  Google Scholar 

  • Caruso DJ, Carmack AJ, Lokeshwar VB, Duncan RC, Soloway MS, Lokeshwar BL (2008) Osteopontin and interleukin-8 expression is independently associated with prostate cancer recurrence. Clin Cancer Res 14(13):4111–4118

    Article  PubMed  CAS  Google Scholar 

  • Cesinaro AM, Migaldi M, Ferrari G, Castagnetti G, Dotti A, De Gaetani C, Ferrari P, Trentini GP (2000) Expression of p53 and bcl-2 in clinically localized prostate cancer before and after neo-adjuvant hormonal therapy. Oncol Res 12(1):43–49

    PubMed  CAS  Google Scholar 

  • Chakravarti A, Heydon K, Wu CL, Hammond E, Pollack A, Roach M, Wolkov H, Okunieff P, Cox J, Fontanesi J, Abrams R, Pilepich M, Shipley W (2003) Loss of p16 expression is of prognostic significance in locally advanced prostate cancer: an analysis from the Radiation Therapy Oncology Group protocol 86–10. J Clin Oncol 21(17):3328–3334

    Article  PubMed  CAS  Google Scholar 

  • Chakravarti A, DeSilvio M, Zhang M, Grignon D, Rosenthal S, Asbell SO, Hanks G, Sandler HM, Khor LY, Pollack A, Shipley W, Radiation Therapy Oncology G (2007) Prognostic value of p16 in locally advanced prostate cancer: a study based on Radiation Therapy Oncology Group Protocol 9202. J Clin Oncol 25(21):3082–3089

    Article  PubMed  Google Scholar 

  • Che M, DeSilvio M, Pollack A, Grignon DJ, Venkatesan VM, Hanks GE, Sandler HM, Rtog (2007) Prognostic value of abnormal p53 expression in locally advanced prostate cancer treated with androgen deprivation and radiotherapy: a study based on RTOG 9202. Int J Radiat Oncol Biol Phys 69(4):1117–1123

    Article  PubMed  CAS  Google Scholar 

  • Cheng L, Pisansky TM, Sebo TJ, Leibovich BC, Ramnani DM, Weaver AL, Scherer BG, Blute ML, Zincke H, Bostwick DG (1999a) Cell proliferation in prostate cancer patients with lymph node metastasis: a marker for progression. Clin Cancer Res 5(10):2820–2823

    PubMed  CAS  Google Scholar 

  • Cheng L, Sebo TJ, Cheville JC, Pisansky TM, Slezak J, Bergstralh EJ, Pacelli A, Neumann RM, Zincke H, Bostwick DG (1999b) p53 protein overexpression is associated with increased cell proliferation in patients with locally recurrent prostate carcinoma after radiation therapy. Cancer 85(6):1293–1299

    Article  PubMed  CAS  Google Scholar 

  • Cheng L, Lloyd RV, Weaver AL, Pisansky TM, Cheville JC, Ramnani DM, Leibovich BC, Blute ML, Zincke H, Bostwick DG (2000) The cell cycle inhibitors p21WAF1 and p27KIP1 are associated with survival in patients treated by salvage prostatectomy after radiation therapy. Clin Cancer Res 6(5):1896–1899

    PubMed  CAS  Google Scholar 

  • Cheville JC, Karnes RJ, Therneau TM, Kosari F, Munz JM, Tillmans L, Basal E, Rangel LJ, Bergstralh E, Kovtun IV, Savci-Heijink CD, Klee EW, Vasmatzis G (2008) Gene panel model predictive of outcome in men at high-risk of systemic progression and death from prostate cancer after radical retropubic prostatectomy. J Clin Oncol 26(24):3930–3936

    Article  PubMed  Google Scholar 

  • Cordon-Cardo C, Kotsianti A, Verbel DA, Teverovskiy M, Capodieci P, Hamann S, Jeffers Y, Clayton M, Elkhettabi F, Khan FM, Sapir M, Bayer-Zubek V, Vengrenyuk Y, Fogarsi S, Saidi O, Reuter VE, Scher HI, Kattan MW, Bianco FJ, Wheeler TM, Ayala GE, Scardino PT, Donovan MJ (2007) Improved prediction of prostate cancer recurrence through systems pathology. J Clin Invest 117(7):1876–1883

    Article  PubMed  CAS  Google Scholar 

  • Cowen D, Troncoso P, Khoo VS, Zagars GK, von Eschenbach AC, Meistrich ML, Pollack A (2002) Ki-67 staining is an independent correlate of biochemical failure in prostate cancer treated with radiotherapy. Clin Cancer Res 8(5):1148–1154

    PubMed  Google Scholar 

  • Dai B, Kong YY, Ye DW, Ma CG, Zhou XY, Yao XD (2008) Human epidermal growth factor receptor type 2 protein expression in Chinese metastatic prostate cancer patients correlates with cancer specific survival and increases after exposure to hormonal therapy. Asian J Androl 10(5):701–709

    Article  PubMed  CAS  Google Scholar 

  • D’Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, Tomaszewski JE, Renshaw AA, Kaplan I, Beard CJ, Wein A (1998) Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 280(11):969–974

    Article  PubMed  Google Scholar 

  • de la Taille A, Katz AE, Bagiella E, Buttyan R, Sharir S, Olsson CA, Burchardt T, Ennis RD, Rubin MA (2000) Microvessel density as a predictor of PSA recurrence after radical prostatectomy. A comparison of CD34 and CD31. Am J Clin Pathol 113(4):555–562

    Article  PubMed  Google Scholar 

  • Deliveliotis C, Skolarikos A, Karayannis A, Tzelepis V, Trakas N, Alargof E, Protogerou V (2003) The prognostic value of p53 and DNA ploidy following radical prostatectomy. World J Urol 21(3):171–176

    Article  PubMed  CAS  Google Scholar 

  • Desai B, Ma T, Zhu J, Chellaiah MA (2009) Characterization of the expression of variant and standard CD44 in prostate cancer cells: identification of the possible molecular mechanism of CD44/MMP9 complex formation on the cell surface. J Cell Biochem 108(1):272–284

    Article  PubMed  CAS  Google Scholar 

  • Di Lorenzo G, Tortora G, D’Armiento FP, De Rosa G, Staibano S, Autorino R, D’Armiento M, De Laurentiis M, De Placido S, Catalano G, Bianco AR, Ciardiello F (2002) Expression of epidermal growth factor receptor correlates with disease relapse and progression to androgen-independence in human prostate cancer. Clin Cancer Res 8(11):3438–3444

    PubMed  Google Scholar 

  • Di Lorenzo G, De Placido S, Autorino R, De Laurentiis M, Mignogna C, D’Armiento M, Tortora G, De Rosa G, De Sio M, Bianco AR, D’Armiento FP (2005) Expression of biomarkers modulating prostate cancer progression: implications in the treatment of the disease. Prostate Cancer Prostatic Dis 8(1):54–59

    Article  PubMed  CAS  Google Scholar 

  • Diallo JS, Aldejmah A, Mouhim AF, Fahmy MA, Koumakpayi IH, Sircar K, Begin LR, Mes-Masson AM, Saad F (2008) Co-assessment of cytoplasmic and nuclear androgen receptor location in prostate specimens: potential implications for prostate cancer development and prognosis. BJU Int 101(10):1302–1309

    Article  PubMed  Google Scholar 

  • Domingo-Domenech J, Mellado B, Ferrer B, Truan D, Codony-Servat J, Sauleda S, Alcover J, Campo E, Gascon P, Rovira A, Ross JS, Fernandez PL, Albanell J (2005) Activation of nuclear factor-kappaB in human prostate carcinogenesis and association to biochemical relapse. Br J Cancer 93(11):1285–1294

    Article  PubMed  CAS  Google Scholar 

  • Donovan MJ, Khan FM, Fernandez G, Mesa-Tejada R, Sapir M, Zubek VB, Powell D, Fogarasi S, Vengrenyuk Y, Teverovskiy M, Segal MR, Karnes RJ, Gaffey TA, Busch C, Haggman M, Hlavcak P, Freedland SJ, Vollmer RT, Albertsen P, Costa J, Cordon-Cardo C (2009) Personalized prediction of tumor response and cancer progression on prostate needle biopsy. J Urol 182(1):125–132

    Article  PubMed  Google Scholar 

  • Donovan MJ, Osman I, Khan FM, Vengrenyuk Y, Capodieci P, Koscuiszka M, Anand A, Cordon-Cardo C, Costa J, Scher HI (2010) Androgen receptor expression is associated with prostate cancer-specific survival in castrate patients with metastatic disease. BJU Int 105(4):462–467

    Article  PubMed  CAS  Google Scholar 

  • Drobnjak M, Melamed J, Taneja S, Melzer K, Wieczorek R, Levinson B, Zeleniuch-Jacquotte A, Polsky D, Ferrara J, Perez-Soler R, Cordon-Cardo C, Pagano M, Osman I (2003) Altered expression of p27 and Skp2 proteins in prostate cancer of African-American patients. Clin Cancer Res 9(7):2613–2619

    PubMed  CAS  Google Scholar 

  • Edwards J, Traynor P, Munro AF, Pirret CF, Dunne B, Bartlett JM (2006) The role of HER1-HER4 and EGFRvIII in hormone-refractory prostate cancer. Clin Cancer Res 12(1):123–130

    Article  PubMed  CAS  Google Scholar 

  • Ekici S, Cerwinka WH, Duncan R, Gomez P, Civantos F, Soloway MS, Lokeshwar VB (2004) Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL-1), CD44v6 and microvessel density for prostate cancer. Int J Cancer 112(1):121–129

    Article  PubMed  CAS  Google Scholar 

  • El Sheikh SS, Romanska HM, Abel P, Domin J, el Lalani N (2008) Predictive value of PTEN and AR coexpression of sustained responsiveness to hormonal therapy in prostate cancer–a pilot study. Neoplasia 10(9):949–953

    PubMed  Google Scholar 

  • Erbersdobler A, Isbarn H, Dix K, Steiner I, Schlomm T, Mirlacher M, Sauter G, Haese A (2010) Prognostic value of microvessel density in prostate cancer: a tissue microarray study. World J Urol 28(6):687–692

    Article  PubMed  Google Scholar 

  • FitzGerald LM, Agalliu I, Johnson K, Miller MA, Kwon EM, Hurtado-Coll A, Fazli L, Rajput AB, Gleave ME, Cox ME, Ostrander EA, Stanford JL, Huntsman DG (2008) Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer. BMC Cancer 8:230

    Article  PubMed  CAS  Google Scholar 

  • Fleischmann A, Schlomm T, Huland H, Kollermann J, Simon P, Mirlacher M, Salomon G, Chun FH, Steuber T, Simon R, Sauter G, Graefen M, Erbersdobler A (2008) Distinct subcellular expression patterns of neutral endopeptidase (CD10) in prostate cancer predict diverging clinical courses in surgically treated patients. Clin Cancer Res 14(23):7838–7842

    Article  PubMed  CAS  Google Scholar 

  • Fossa A, Lilleby W, Fossa SD, Gaudernack G, Torlakovic G, Berner A (2002) Independent prognostic significance of HER-2 oncoprotein expression in pN0 prostate cancer undergoing curative radiotherapy. Int J Cancer 99(1):100–105

    Article  PubMed  CAS  Google Scholar 

  • Fradet V, Lessard L, Begin LR, Karakiewicz P, Masson AM, Saad F (2004) Nuclear factor-kappaB nuclear localization is predictive of biochemical recurrence in patients with positive margin prostate cancer. Clin Cancer Res 10(24):8460–8464

    Article  PubMed  CAS  Google Scholar 

  • Freedland SJ, deGregorio F, Sacoolidge JC, Elshimali YI, Csathy GS, Dorey F, Reiter RE, Aronson WJ (2003) Preoperative p27 status is an independent predictor of prostate specific antigen failure following radical prostatectomy. J Urol 169(4):1325–1330

    Article  PubMed  CAS  Google Scholar 

  • Fukuda H, Tsuchiya N, Narita S, Kumazawa T, Horikawa Y, Inoue T, Saito M, Yuasa T, Matsuura S, Satoh S, Ogawa O, Habuchi T (2007) Clinical implication of vascular endothelial growth factor T-460C polymorphism in the risk and progression of prostate cancer. Oncol Rep 18(5):1155–1163

    PubMed  CAS  Google Scholar 

  • Furusato B, Shaheduzzaman S, Petrovics G, Dobi A, Seifert M, Ravindranath L, Nau ME, Werner T, Vahey M, McLeod DG, Srivastava S, Sesterhenn IA (2008) Transcriptome analyses of benign and malignant prostate epithelial cells in formalin-fixed paraffin-embedded whole-mounted radical prostatectomy specimens. Prostate Cancer Prostatic Dis 11(2):194–197

    Article  PubMed  CAS  Google Scholar 

  • Gallucci M, Merola R, Leonardo C, De Carli P, Farsetti A, Sentinelli S, Sperduti I, Mottolese M, Carlini P, Vico E, Simone G, Cianciulli A (2009) Genetic profile identification in clinically localized prostate carcinoma. Urol Oncol 27(5):502–508

    Article  PubMed  CAS  Google Scholar 

  • Girvan AR, Chang P, van Huizen I, Moussa M, Xuan JW, Stitt L, Chin JL, Yamasaki Y, Izawa JI (2005) Increased intratumoral expression of prostate secretory protein of 94 amino acids predicts for worse disease recurrence and progression after radical prostatectomy in patients with prostate cancer. Urology 65(4):719–723

    Article  PubMed  Google Scholar 

  • Glinsky GV, Glinskii AB, Stephenson AJ, Hoffman RM, Gerald WL (2004) Gene expression profiling predicts clinical outcome of prostate cancer. J Clin Invest 113(6):913–923

    PubMed  CAS  Google Scholar 

  • Goto T, Nguyen BP, Nakano M, Ehara H, Yamamoto N, Deguchi T (2008) Utility of Bcl-2, P53, Ki-67, and caveolin-1 immunostaining in the prediction of biochemical failure after radical prostatectomy in a Japanese population. Urology 72(1):167–171

    Article  PubMed  Google Scholar 

  • Gravdal K, Halvorsen OJ, Haukaas SA, Akslen LA (2006) Expression of bFGF/FGFR-1 and vascular proliferation related to clinicopathologic features and tumor progress in localized prostate cancer. Virchows Arch 448(1):68–74

    Article  PubMed  CAS  Google Scholar 

  • Gravdal K, Halvorsen OJ, Haukaas SA, Akslen LA (2009) Proliferation of immature tumor vessels is a novel marker of clinical progression in prostate cancer. Cancer Res 69(11):4708–4715

    Article  PubMed  CAS  Google Scholar 

  • Gunia S, Albrecht K, Koch S, Herrmann T, Ecke T, Loy V, Linke J, Siegsmund M, May M (2008) Ki67 staining index and neuroendocrine differentiation aggravate adverse prognostic parameters in prostate cancer and are characterized by negligible inter-observer variability. World J Urol 26(3):243–250

    Article  PubMed  Google Scholar 

  • Gupta A, Lotan Y, Ashfaq R, Roehrborn CG, Raj GV, Aragaki CC, Montorsi F, Shariat SF (2009) Predictive value of the differential expression of the urokinase plasminogen activation axis in radical prostatectomy patients. Eur Urol 55(5):1124–1133

    Article  PubMed  CAS  Google Scholar 

  • Halvorsen OJ, Haukaas S, Hoisaeter PA, Akslen LA (2000a) Independent prognostic importance of microvessel density in clinically localized prostate cancer. Anticancer Res 20(5C):3791–3799

    PubMed  CAS  Google Scholar 

  • Halvorsen OJ, Hostmark J, Haukaas S, Hoisaeter PA, Akslen LA (2000b) Prognostic significance of p16 and CDK4 proteins in localized prostate carcinoma. Cancer 88(2):416–424

    Article  PubMed  CAS  Google Scholar 

  • Halvorsen OJ, Haukaas S, Hoisaeter PA, Akslen LA (2001) Maximum Ki-67 staining in prostate cancer provides independent prognostic information after radical prostatectomy. Anticancer Res 21(6A):4071–4076

    PubMed  CAS  Google Scholar 

  • Halvorsen OJ, Haukaas SA, Akslen LA (2003) Combined loss of PTEN and p27 expression is associated with tumor cell proliferation by Ki-67 and increased risk of recurrent disease in localized prostate cancer. Clin Cancer Res 9(4):1474–1479

    PubMed  CAS  Google Scholar 

  • Hassan MI, Waheed A, Yadav S, Singh TP, Ahmad F (2008) Zinc alpha 2-glycoprotein: a multidisciplinary protein. Mol Cancer Res 6(6):892–906

    Article  PubMed  CAS  Google Scholar 

  • Hawksworth D, Ravindranath L, Chen Y, Furusato B, Sesterhenn IA, McLeod DG, Srivastava S, Petrovics G (2010) Overexpression of C-MYC oncogene in prostate cancer predicts biochemical recurrence. Prostate Cancer Prostatic Dis 13(4):311–315

    Article  PubMed  CAS  Google Scholar 

  • Heidenreich A, Bellmunt J, Bolla M, Joniau S, Mason M, Matveev V, Mottet N, Schmid HP, van der Kwast T, Wiegel T, Zattoni F (2011) EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Eur Urol 59(1):61–71

    Article  PubMed  Google Scholar 

  • Henshall SM, Quinn DI, Lee CS, Head DR, Golovsky D, Brenner PC, Delprado W, Stricker PD, Grygiel JJ, Sutherland RL (2001a) Altered expression of androgen receptor in the malignant epithelium and adjacent stroma is associated with early relapse in prostate cancer. Cancer Res 61(2):423–427

    PubMed  CAS  Google Scholar 

  • Henshall SM, Quinn DI, Lee CS, Head DR, Golovsky D, Brenner PC, Delprado W, Stricker PD, Grygiel JJ, Sutherland RL (2001b) Overexpression of the cell cycle inhibitor p16INK4A in high-grade prostatic intraepithelial neoplasia predicts early relapse in prostate cancer patients. Clin Cancer Res 7(3):544–550

    PubMed  CAS  Google Scholar 

  • Henshall SM, Horvath LG, Quinn DI, Eggleton SA, Grygiel JJ, Stricker PD, Biankin AV, Kench JG, Sutherland RL (2006) Zinc-alpha2-glycoprotein expression as a predictor of metastatic prostate cancer following radical prostatectomy. J Natl Cancer Inst 98(19):1420–1424

    Article  PubMed  CAS  Google Scholar 

  • Hermans KG, Boormans JL, Gasi D, van Leenders GJ, Jenster G, Verhagen PC, Trapman J (2009) Overexpression of prostate-specific TMPRSS2(exon 0)-ERG fusion transcripts corresponds with favorable prognosis of prostate cancer. Clin Cancer Res 15(20):6398–6403

    Article  PubMed  CAS  Google Scholar 

  • Hernes E, Fossa SD, Berner A, Otnes B, Nesland JM (2004) Expression of the epidermal growth factor receptor family in prostate carcinoma before and during androgen-independence. Br J Cancer 90(2):449–454

    Article  PubMed  CAS  Google Scholar 

  • Hintz BL, Koo C, Murphy JF (2004) Pattern of proliferative index (Ki-67) after anti-androgen manipulation reflects the ability of irradiation to control prostate cancer. Am J Clin Oncol 27(1):85–88

    Article  PubMed  Google Scholar 

  • Hirata H, Hinoda Y, Kikuno N, Suehiro Y, Shahryari V, Ahmad AE, Tabatabai ZL, Igawa M, Dahiya R (2009) Bcl2 -938C/A polymorphism carries increased risk of biochemical recurrence after radical prostatectomy. J Urol 181(4):1907–1912

    Article  PubMed  CAS  Google Scholar 

  • Hori S, Jabbar T, Kachroo N, Vasconcelos JC, Robson CN, Gnanapragasam VJ (2011) Outcomes and predictive factors for biochemical relapse following primary androgen deprivation therapy in men with bone scan negative prostate cancer. J Cancer Res Clin Oncol 137(2):235–241

    Article  PubMed  CAS  Google Scholar 

  • Horvath LG, Henshall SM, Lee CS, Head DR, Quinn DI, Makela S, Delprado W, Golovsky D, Brenner PC, O’Neill G, Kooner R, Stricker PD, Grygiel JJ, Gustafsson JA, Sutherland RL (2001) Frequent loss of estrogen receptor-beta expression in prostate cancer. Cancer Res 61(14):5331–5335

    PubMed  CAS  Google Scholar 

  • Huang SP, Huang CY, Wang JS, Liu CC, Pu YS, Yu HJ, Yu CC, Wu TT, Huang CH, Wu WJ, Chou YH, Wu MT (2007) Prognostic significance of p53 and X-ray repair cross-complementing group 1 polymorphisms on prostate-specific antigen recurrence in prostate cancer post radical prostatectomy. Clin Cancer Res 13(22 Pt 1):6632–6638

    Article  PubMed  CAS  Google Scholar 

  • Incognito LS, Cazares LH, Schellhammer PF, Kuban DA, Van Dyk EO, Moriarty RP, Wright GL Jr, Somers KD (2000) Overexpression of p53 in prostate carcinoma is associated with improved overall survival but not predictive of response to radiotherapy. Int J Oncol 17(4):761–769

    PubMed  CAS  Google Scholar 

  • Inoue T, Segawa T, Shiraishi T, Yoshida T, Toda Y, Yamada T, Kinukawa N, Kinoshita H, Kamoto T, Ogawa O (2005) Androgen receptor, Ki67, and p53 expression in radical prostatectomy specimens predict treatment failure in Japanese population. Urology 66(2):332–337

    Article  PubMed  Google Scholar 

  • Isharwal S, Miller MC, Epstein JI, Mangold LA, Humphreys E, Partin AW, Veltri RW (2008) Prognostic value of Her-2/neu and DNA index for progression, metastasis and prostate cancer-specific death in men with long-term follow-up after radical prostatectomy. Int J Cancer 123(11):2636–2643

    Article  PubMed  CAS  Google Scholar 

  • Jack RH, Davies EA, Moller H (2010) Prostate cancer incidence, stage at diagnosis, treatment and survival in ethnic groups in South-East England. BJU Int 105(9):1226–1230

    Article  PubMed  Google Scholar 

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90

    Article  PubMed  Google Scholar 

  • Kamiya N, Suzuki H, Kawamura K, Imamoto T, Naya Y, Tochigi N, Kakuta Y, Yamaguchi K, Ishikura H, Ichikawa T (2008) Neuroendocrine differentiation in stage D2 prostate cancers. Int J Urol 15(5):423–428

    Article  PubMed  CAS  Google Scholar 

  • Karam JA, Lotan Y, Roehrborn CG, Ashfaq R, Karakiewicz PI, Shariat SF (2007) Caveolin-1 overexpression is associated with aggressive prostate cancer recurrence. Prostate 67(6):614–622

    Article  PubMed  Google Scholar 

  • Kawakami J, Cowan JE, Elkin EP, Latini DM, DuChane J, Carroll PR (2006) Androgen-deprivation therapy as primary treatment for localized prostate cancer: data from Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). Cancer 106(8):1708–1714

    Article  PubMed  Google Scholar 

  • Khatami A, Pihl CG, Norrby K, Hugosson J, Damber JE (2005) Is tumor vascularity in prostate core biopsies a predictor of PSA recurrence after radical prostatectomy? Acta Oncol 44(4):362–368

    Article  PubMed  Google Scholar 

  • Khor LY, Bae K, Pollack A, Hammond ME, Grignon DJ, Venkatesan VM, Rosenthal SA, Ritter MA, Sandler HM, Hanks GE, Shipley WU, Dicker AP (2007a) COX-2 expression predicts prostate-cancer outcome: analysis of data from the RTOG 92–02 trial. Lancet Oncol 8(10):912–920

    Article  PubMed  CAS  Google Scholar 

  • Khor LY, Moughan J, Al-Saleem T, Hammond EH, Venkatesan V, Rosenthal SA, Ritter MA, Sandler HM, Hanks GE, Shipley WU, Pollack A (2007b) Bcl-2 and Bax expression predict prostate cancer outcome in men treated with androgen deprivation and radiotherapy on radiation therapy oncology group protocol 92–02. Clin Cancer Res 13(12):3585–3590

    Article  PubMed  CAS  Google Scholar 

  • Khor LY, Bae K, Al-Saleem T, Hammond EH, Grignon DJ, Sause WT, Pilepich MV, Okunieff PP, Sandler HM, Pollack A (2008) Protein kinase A RI-alpha predicts for prostate cancer outcome: analysis of radiation therapy oncology group trial 86–10. Int J Radiat Oncol Biol Phys 71(5):1309–1315

    Article  PubMed  CAS  Google Scholar 

  • Khor LY, Bae K, Paulus R, Al-Saleem T, Hammond ME, Grignon DJ, Che M, Venkatesan V, Byhardt RW, Rotman M, Hanks GE, Sandler HM, Pollack A (2009) MDM2 and Ki-67 predict for distant metastasis and mortality in men treated with radiotherapy and androgen deprivation for prostate cancer: RTOG 92–02. J Clin Oncol 27(19):3177–3184

    Article  PubMed  Google Scholar 

  • Koumakpayi IH, Le Page C, Mes-Masson AM, Saad F (2010) Hierarchical clustering of immunohistochemical analysis of the activated ErbB/PI3 K/Akt/NF-kappaB signalling pathway and prognostic significance in prostate cancer. Br J Cancer 102(7):1163–1173

    Article  PubMed  CAS  Google Scholar 

  • Krupski T, Petroni GR, Frierson HF Jr, Theodorescu JU (2000) Microvessel density, p53, retinoblastoma, and chromogranin A immunohistochemistry as predictors of disease-specific survival following radical prostatectomy for carcinoma of the prostate. Urology 55(5):743–749

    Article  PubMed  CAS  Google Scholar 

  • Kuczyk M, Machtens S (1999) Predictive value of decreased p27 Kip1 protein expression for the recurrence-free and long-term survival of prostate cancer patients. Prostate Cancer Prostatic Dis 2(S3):S17

    Article  PubMed  Google Scholar 

  • Kuczyk M, Serth J, Machtens S, Bokemeyer C, Bathke W, Stief C, Jonas U (1998) Expression of E-cadherin in primary prostate cancer: correlation with clinical features. Br J Urol 81(3):406–412

    Article  PubMed  CAS  Google Scholar 

  • Kuczyk MA, Bokemeyer C, Hartmann J, Schubach J, Walter C, Machtens S, Knuchel R, Kollmannsberger C, Jonas U, Serth J (2001) Predictive value of altered p27Kip1 and p21WAF/Cip1 protein expression for the clinical prognosis of patients with localized prostate cancer. Oncol Rep 8(6):1401–1407

    PubMed  CAS  Google Scholar 

  • Kumano M, Miyake H, Muramaki M, Furukawa J, Takenaka A, Fujisawa M (2009) Expression of urokinase-type plasminogen activator system in prostate cancer: correlation with clinicopathological outcomes in patients undergoing radical prostatectomy. Urol Oncol 27(2):180–186

    Article  PubMed  CAS  Google Scholar 

  • Lacombe L, Maillette A, Meyer F, Veilleux C, Moore L, Fradet Y (2001) Expression of p21 predicts PSA failure in locally advanced prostate cancer treated by prostatectomy. Int J Cancer 95(3):135–139

    Article  PubMed  CAS  Google Scholar 

  • Laitinen S, Martikainen PM, Tolonen T, Isola J, Tammela TL, Visakorpi T (2008) EZH2, Ki-67 and MCM7 are prognostic markers in prostatectomy treated patients. Int J Cancer 122(3):595–602

    Article  PubMed  CAS  Google Scholar 

  • Lapointe J, Li C, Higgins JP, van de Rijn M, Bair E, Montgomery K, Ferrari M, Egevad L, Rayford W, Bergerheim U, Ekman P, DeMarzo AM, Tibshirani R, Botstein D, Brown PO, Brooks JD, Pollack JR (2004) Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci U S A 101(3):811–816

    Article  PubMed  CAS  Google Scholar 

  • Lapointe J, Kim YH, Miller MA, Li C, Kaygusuz G, van de Rijn M, Huntsman DG, Brooks JD, Pollack JR (2007) A variant TMPRSS2 isoform and ERG fusion product in prostate cancer with implications for molecular diagnosis. Mod Pathol 20(4):467–473

    Article  PubMed  CAS  Google Scholar 

  • Le Page C, Koumakpayi IH, Alam-Fahmy M, Mes-Masson AM, Saad F (2006) Expression and localisation of Akt-1, Akt-2 and Akt-3 correlate with clinical outcome of prostate cancer patients. Br J Cancer 94(12):1906–1912

    Article  PubMed  CAS  Google Scholar 

  • Lee CT, Capodieci P, Osman I, Fazzari M, Ferrara J, Scher HI, Cordon-Cardo C (1999) Overexpression of the cyclin-dependent kinase inhibitor p16 is associated with tumor recurrence in human prostate cancer. Clin Cancer Res 5(5):977–983

    PubMed  CAS  Google Scholar 

  • Leibovich BC, Cheng L, Weaver AL, Myers RP, Bostwick DG (2000) Outcome prediction with p53 immunostaining after radical prostatectomy in patients with locally advanced prostate cancer. J Urol 163(6):1756–1760

    Article  PubMed  CAS  Google Scholar 

  • Li R, Heydon K, Hammond ME, Grignon DJ, Roach M 3rd, Wolkov HB, Sandler HM, Shipley WU, Pollack A (2004a) Ki-67 staining index predicts distant metastasis and survival in locally advanced prostate cancer treated with radiotherapy: an analysis of patients in radiation therapy oncology group protocol 86–10. Clin Cancer Res 10(12 Pt 1):4118–4124

    Article  PubMed  CAS  Google Scholar 

  • Li R, Wheeler T, Dai H, Frolov A, Thompson T, Ayala G (2004b) High level of androgen receptor is associated with aggressive clinicopathologic features and decreased biochemical recurrence-free survival in prostate: cancer patients treated with radical prostatectomy. Am J Surg Pathol 28(7):928–934

    Article  PubMed  Google Scholar 

  • Li R, Wheeler TM, Dai H, Sayeeduddin M, Scardino PT, Frolov A, Ayala GE (2006) Biological correlates of p27 compartmental expression in prostate cancer. J Urol 175(2):528–532

    Article  PubMed  CAS  Google Scholar 

  • Li R, Dai H, Wheeler TM, Sayeeduddin M, Scardino PT, Frolov A, Ayala GE (2009) Prognostic value of Akt-1 in human prostate cancer: a computerized quantitative assessment with quantum dot technology. Clin Cancer Res 15(10):3568–3573

    Article  PubMed  CAS  Google Scholar 

  • Loric S, Paradis V, Gala JL, Berteau P, Bedossa P, Benoit G, Eschwege P (2001) Abnormal E-cadherin expression and prostate cell blood dissemination as markers of biological recurrence in cancer. Eur J Cancer 37(12):1475–1481

    Article  PubMed  CAS  Google Scholar 

  • Matsuura H, Hayashi N, Kawamura J, Shiraishi T, Yatani R (2000) Prognostic significance of Ki-67 expression in advanced prostate cancers in relation to disease progression after androgen ablation. Eur Urol 37(2):212–217

    Article  PubMed  CAS  Google Scholar 

  • May M, Siegsmund M, Hammermann F, Loy V, Gunia S (2007) Prognostic significance of proliferation activity and neuroendocrine differentiation to predict treatment failure after radical prostatectomy. Scand J Urol Nephrol 41(5):375–381

    Article  PubMed  CAS  Google Scholar 

  • McCall P, Witton CJ, Grimsley S, Nielsen KV, Edwards J (2008) Is PTEN loss associated with clinical outcome measures in human prostate cancer? Br J Cancer 99(8):1296–1301

    Article  PubMed  CAS  Google Scholar 

  • Minner S, Jessen B, Stiedenroth L, Burandt E, Kollermann J, Mirlacher M, Erbersdobler A, Eichelberg C, Fisch M, Brummendorf TH, Bokemeyer C, Simon R, Steuber T, Graefen M, Huland H, Sauter G, Schlomm T (2010) Low level HER2 overexpression is associated with rapid tumor cell proliferation and poor prognosis in prostate cancer. Clin Cancer Res 16(5):1553–1560

    Article  PubMed  CAS  Google Scholar 

  • Miyake H, Muramaki M, Kurahashi T, Takenaka A, Fujisawa M (2010) Expression of potential molecular markers in prostate cancer: correlation with clinicopathological outcomes in patients undergoing radical prostatectomy. Urol Oncol 28(2):145–151

    Article  PubMed  CAS  Google Scholar 

  • Mottet N, Bellmunt J, Bolla M, Joniau S, Mason M, Matveev V, Schmid HP, Van der Kwast T, Wiegel T, Zattoni F, Heidenreich A (2011) EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol 59(4):572–583

    Article  PubMed  Google Scholar 

  • Mucci LA, Pawitan Y, Demichelis F, Fall K, Stark JR, Adami HO, Andersson SO, Andren O, Eisenstein AS, Holmberg L, Huang W, Kantoff PW, Perner S, Stampfer MJ, Johansson JE, Rubin MA (2008) Nine-gene molecular signature is not associated with prostate cancer death in a watchful waiting cohort. Cancer Epidemiol Biomarkers Prev 17(1):249–251

    Article  PubMed  CAS  Google Scholar 

  • Nakagawa T, Kollmeyer TM, Morlan BW, Anderson SK, Bergstralh EJ, Davis BJ, Asmann YW, Klee GG, Ballman KV, Jenkins RB (2008) A tissue biomarker panel predicting systemic progression after PSA recurrence post-definitive prostate cancer therapy. PLoS ONE 3(5):e2318

    Article  PubMed  CAS  Google Scholar 

  • Nam RK, Sugar L, Yang W, Srivastava S, Klotz LH, Yang LY, Stanimirovic A, Encioiu E, Neill M, Loblaw DA, Trachtenberg J, Narod SA, Seth A (2007) Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer. Br J Cancer 97(12):1690–1695

    Article  PubMed  CAS  Google Scholar 

  • Nanni S, Benvenuti V, Grasselli A, Priolo C, Aiello A, Mattiussi S, Colussi C, Lirangi V, Illi B, D’Eletto M, Cianciulli AM, Gallucci M, De Carli P, Sentinelli S, Mottolese M, Carlini P, Strigari L, Finn S, Mueller E, Arcangeli G, Gaetano C, Capogrossi MC, Donnorso RP, Bacchetti S, Sacchi A, Pontecorvi A, Loda M, Farsetti A (2009) Endothelial NOS, estrogen receptor beta, and HIFs cooperate in the activation of a prognostic transcriptional pattern in aggressive human prostate cancer. J Clin Invest 119(5):1093–1108

    Article  PubMed  CAS  Google Scholar 

  • Nariculam J, Freeman A, Bott S, Munson P, Cable N, Brookman-Amissah N, Williamson M, Kirby RS, Masters J, Feneley M (2009) Utility of tissue microarrays for profiling prognostic biomarkers in clinically localized prostate cancer: the expression of BCL-2, E-cadherin, Ki-67 and p53 as predictors of biochemical failure after radical prostatectomy with nested control for clinical and pathological risk factors. Asian J Androl 11(1):109–118

    Article  PubMed  CAS  Google Scholar 

  • Nelson PS (2004) Predicting prostate cancer behavior using transcript profiles. J Urol 172 (5 Pt 2):S28–32; discussion S33

  • Neto AS, Tobias-Machado M, Wroclawski ML, Fonseca FL, Teixeira GK, Amarante RD, Wroclawski ER, Del Giglio A (2010) Her-2/neu expression in prostate adenocarcinoma: a systematic review and meta-analysis. J Urol 184(3):842–850

    Article  PubMed  CAS  Google Scholar 

  • Nikoleishvili D, Pertia A, Trsintsadze O, Gogokhia N, Managadze L, Chkhotua A (2008) Expression of p27((Kip1)), cyclin D3 and Ki67 in BPH, prostate cancer and hormone-treated prostate cancer cells. Int Urol Nephrol 40(4):953–959

    Article  PubMed  CAS  Google Scholar 

  • Omar EA, Behlouli H, Chevalier S, Aprikian AG (2001) Relationship of p21(WAF-I) protein expression with prognosis in advanced prostate cancer treated by androgen ablation. Prostate 49(3):191–199

    Article  PubMed  CAS  Google Scholar 

  • Osman I, Drobnjak M, Fazzari M, Ferrara J, Scher HI, Cordon-Cardo C (1999) Inactivation of the p53 pathway in prostate cancer: impact on tumor progression. Clin Cancer Res 5(8):2082–2088

    PubMed  CAS  Google Scholar 

  • Osman I, Yee H, Taneja SS, Levinson B, Zeleniuch-Jacquotte A, Chang C, Nobert C, Nanus DM (2004) Neutral endopeptidase protein expression and prognosis in localized prostate cancer. Clin Cancer Res 10(12 Pt 1):4096–4100

    Article  PubMed  CAS  Google Scholar 

  • Osman I, Dai J, Mikhail M, Navarro D, Taneja SS, Lee P, Christos P, Shen R, Nanus DM (2006) Loss of neutral endopeptidase and activation of protein kinase B (Akt) is associated with prostate cancer progression. Cancer 107(11):2628–2636

    Article  PubMed  CAS  Google Scholar 

  • Oxley JD, Winkler MH, Parry K, Brewster S, Abbott C, Gillatt DA (2002) p53 and bcl-2 immunohistochemistry in preoperative biopsies as predictors of biochemical recurrence after radical prostatectomy. BJU Int 89(1):27–32

    Article  PubMed  CAS  Google Scholar 

  • Perez CA, Chen H, Shyr Y, Courtney R, Zheng W, Cai Q, Hwang M, Jaboin J, Schleicher S, Moretti L, Wills M, Smith JA, Lu B (2010) The EGFR polymorphism rs884419 is associated with freedom from recurrence in patients with resected prostate cancer. J Urol 183(5):2062–2069

    Article  PubMed  CAS  Google Scholar 

  • Pollack A, Cowen D, Troncoso P, Zagars GK, von Eschenbach AC, Meistrich ML, McDonnell T (2003a) Molecular markers of outcome after radiotherapy in patients with prostate carcinoma: Ki-67, bcl-2, bax, and bcl-x. Cancer 97(7):1630–1638

    Article  PubMed  Google Scholar 

  • Pollack A, Grignon DJ, Heydon KH, Hammond EH, Lawton CA, Mesic JB, Fu KK, Porter AT, Abrams RA, Shipley WU (2003b) Prostate cancer DNA ploidy and response to salvage hormone therapy after radiotherapy with or without short-term total androgen blockade: an analysis of RTOG 8610. J Clin Oncol 21(7):1238–1248

    Article  PubMed  CAS  Google Scholar 

  • Pollack A, DeSilvio M, Khor LY, Li R, Al-Saleem TI, Hammond ME, Venkatesan V, Lawton CA, Roach M 3rd, Shipley WU, Hanks GE, Sandler HM (2004) Ki-67 staining is a strong predictor of distant metastasis and mortality for men with prostate cancer treated with radiotherapy plus androgen deprivation: radiation Therapy Oncology Group Trial 92–02. J Clin Oncol 22(11):2133–2140

    Article  PubMed  CAS  Google Scholar 

  • Pollack A, Bae K, Khor LY, Al-Saleem T, Hammond ME, Venkatesan V, Byhardt RW, Asbell SO, Shipley WU, Sandler HM (2009) The importance of protein kinase A in prostate cancer: relationship to patient outcome in Radiation Therapy Oncology Group trial 92–02. Clin Cancer Res 15(17):5478–5484

    Article  PubMed  CAS  Google Scholar 

  • Quinn DI, Henshall SM, Head DR, Golovsky D, Wilson JD, Brenner PC, Turner JJ, Delprado W, Finlayson JF, Stricker PD, Grygiel JJ, Sutherland RL (2000) Prognostic significance of p53 nuclear accumulation in localized prostate cancer treated with radical prostatectomy. Cancer Res 60(6):1585–1594

    PubMed  CAS  Google Scholar 

  • Rakozy C, Grignon DJ, Li Y, Gheiler E, Gururajanna B, Pontes JE, Sakr W, Wood DP Jr, Sarkar FH (1999) p53 gene alterations in prostate cancer after radiation failure and their association with clinical outcome: a molecular and immunohistochemical analysis. Pathol Res Pract 195(3):129–135

    Article  PubMed  CAS  Google Scholar 

  • Ray ME, Mehra R, Sandler HM, Daignault S, Shah RB (2006) E-cadherin protein expression predicts prostate cancer salvage radiotherapy outcomes. J Urol 176 (4 Pt 1):1409–1414; discussion 1414

    Google Scholar 

  • Revelos K, Petraki C, Gregorakis A, Scorilas A, Papanastasiou P, Koutsilieris M (2005a) Immunohistochemical expression of Bcl2 is an independent predictor of time-to-biochemical failure in patients with clinically localized prostate cancer following radical prostatectomy. Anticancer Res 25(4):3123–3133

    PubMed  CAS  Google Scholar 

  • Revelos K, Petraki C, Gregorakis A, Scorilas A, Papanastasiou P, Tenta R, Koutsilieris M (2005b) p27(kip1) and Ki-67 (MIB1) immunohistochemical expression in radical prostatectomy specimens of patients with clinically localized prostate cancer. In Vivo 19(5):911–920

    PubMed  CAS  Google Scholar 

  • Revelos K, Petraki C, Scorilas A, Stefanakis S, Malovrouvas D, Alevizopoulos N, Kanellis G, Halapas A, Koutsilieris M (2007) Correlation of androgen receptor status, neuroendocrine differentiation and angiogenesis with time-to-biochemical failure after radical prostatectomy in clinically localized prostate cancer. Anticancer Res 27(5B):3651–3660

    Google Scholar 

  • Rhodes DR, Sanda MG, Otte AP, Chinnaiyan AM, Rubin MA (2003) Multiplex biomarker approach for determining risk of prostate-specific antigen-defined recurrence of prostate cancer. J Natl Cancer Inst 95(9):661–668

    Article  PubMed  CAS  Google Scholar 

  • Ribal MJ, Fernandez PL, Lopez-Guillermo A, Farre X, Santos Y, Gibanel R, Cardesa A, Alcaraz A (2003) Low p27 expression predicts biochemical relapse after radical prostatectomy in patients with clinically localised prostate cancer. Anticancer Res 23(6D): 5101–5106

    Google Scholar 

  • Ricciardelli C, Jackson MW, Choong CS, Stahl J, Marshall VR, Horsfall DJ, Tilley WD (2008) Elevated levels of HER-2/neu and androgen receptor in clinically localized prostate cancer identifies metastatic potential. Prostate 68(8):830–838. doi:10.1002/pros.20747

    Article  PubMed  CAS  Google Scholar 

  • Richmond PJ, Karayiannakis AJ, Nagafuchi A, Kaisary AV, Pignatelli M (1997) Aberrant E-cadherin and alpha-catenin expression in prostate cancer: correlation with patient survival. Cancer Res 57(15):3189–3193

    PubMed  CAS  Google Scholar 

  • Rigaud J, Tiguert R, Decobert M, Hovington H, Latulippe E, Laverdiere J, Larue H, Lacombe L, Fradet Y (2004) Expression of p21 cell cycle protein is an independent predictor of response to salvage radiotherapy after radical prostatectomy. Prostate 58(3):269–276

    Article  PubMed  CAS  Google Scholar 

  • Ritter MA, Gilchrist KW, Voytovich M, Chappell RJ, Verhoven BM (2002) The role of p53 in radiation therapy outcomes for favorable-to-intermediate-risk prostate cancer. Int J Radiat Oncol Biol Phys 53(3):574–580

    Article  PubMed  CAS  Google Scholar 

  • Ross JS, Kaur P, Sheehan CE, Fisher HA, Kaufman RA Jr, Kallakury BV (2003) Prognostic significance of matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expression in prostate cancer. Mod Pathol 16(3):198–205

    Article  PubMed  Google Scholar 

  • Ross JS, Kallakury BV, Sheehan CE, Fisher HA, Kaufman RP Jr, Kaur P, Gray K, Stringer B (2004) Expression of nuclear factor-kappa B and I kappa B alpha proteins in prostatic adenocarcinomas: correlation of nuclear factor-kappa B immunoreactivity with disease recurrence. Clin Cancer Res 10(7):2466–2472

    Article  PubMed  CAS  Google Scholar 

  • Rosser CJ, Reyes AO, Vakar-Lopez F, Levy LB, Kuban DA, Hoover DC, Lee AK, Pisters LL (2003) Bcl-2 is significantly overexpressed in localized radio-recurrent prostate carcinoma, compared with localized radio-naive prostate carcinoma. Int J Radiat Oncol Biol Phys 56(1):1–6

    Article  PubMed  CAS  Google Scholar 

  • Roth TJ, Sheinin Y, Lohse CM, Kuntz SM, Frigola X, Inman BA, Krambeck AE, McKenney ME, Karnes RJ, Blute ML, Cheville JC, Sebo TJ, Kwon ED (2007) B7–H3 ligand expression by prostate cancer: a novel marker of prognosis and potential target for therapy. Cancer Res 67(16):7893–7900

    Article  PubMed  CAS  Google Scholar 

  • Rubin MA, Buyyounouski M, Bagiella E, Sharir S, Neugut A, Benson M, de la Taille A, Katz AE, Olsson CA, Ennis RD (1999) Microvessel density in prostate cancer: lack of correlation with tumor grade, pathologic stage, and clinical outcome. Urology 53(3):542–547

    Article  PubMed  CAS  Google Scholar 

  • Rubio J, Ramos D, Lopez-Guerrero JA, Iborra I, Collado A, Solsona E, Almenar S, Llombart-Bosch A (2005) Immunohistochemical expression of Ki-67 antigen, cox-2 and Bax/Bcl-2 in prostate cancer; prognostic value in biopsies and radical prostatectomy specimens. Eur Urol 48(5):745–751

    Article  PubMed  CAS  Google Scholar 

  • Rubio-Briones J, Fernandez-Serra A, Calatrava A, Garcia-Casado Z, Rubio L, Bonillo MA, Iborra I, Solsona E, Lopez-Guerrero JA (2010) Clinical implications of TMPRSS2-ERG gene fusion expression in patients with prostate cancer treated with radical prostatectomy. J Urol 183(5):2054–2061

    Article  PubMed  CAS  Google Scholar 

  • Saramaki OR, Harjula AE, Martikainen PM, Vessella RL, Tammela TL, Visakorpi T (2008) TMPRSS2:ERG fusion identifies a subgroup of prostate cancers with a favorable prognosis. Clin Cancer Res 14(11):3395–3400

    Article  PubMed  Google Scholar 

  • Sato K, Qian J, Slezak JM, Lieber MM, Bostwick DG, Bergstralh EJ, Jenkins RB (1999) Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma. J Natl Cancer Inst 91(18):1574–1580

    Article  PubMed  CAS  Google Scholar 

  • Satoh T, Yang G, Egawa S, Addai J, Frolov A, Kuwao S, Timme TL, Baba S, Thompson TC (2003) Caveolin-1 expression is a predictor of recurrence-free survival in pT2N0 prostate carcinoma diagnosed in Japanese patients. Cancer 97(5):1225–1233

    Article  PubMed  CAS  Google Scholar 

  • Schafer W, Funke PJ, Kunde D, Rausch U, Wennemuth G, Stutzer H (2006) Intensity of androgen and epidermal growth factor receptor immunoreactivity in samples of radical prostatectomy as prognostic indicator: correlation with clinical data of long-term observations. J Urol 176(2):532–537

    Article  PubMed  CAS  Google Scholar 

  • Scherr DS, Vaughan ED, Jr., Wei J, Chung M, Felsen D, Allbright R, Knudsen BS (1999) BCL-2 and p53 expression in clinically localized prostate cancer predicts response to external beam radiotherapy. J Urol 162 (1):12–16; discussion 16–17

    Google Scholar 

  • Schlomm T, Kirstein P, Iwers L, Daniel B, Steuber T, Walz J, Chun FH, Haese A, Kollermann J, Graefen M, Huland H, Sauter G, Simon R, Erbersdobler A (2007) Clinical significance of epidermal growth factor receptor protein overexpression and gene copy number gains in prostate cancer. Clin Cancer Res 13(22 Pt 1):6579–6584

    Article  PubMed  CAS  Google Scholar 

  • Schlomm T, Iwers L, Kirstein P, Jessen B, Kollermann J, Minner S, Passow-Drolet A, Mirlacher M, Milde-Langosch K, Graefen M, Haese A, Steuber T, Simon R, Huland H, Sauter G, Erbersdobler A (2008) Clinical significance of p53 alterations in surgically treated prostate cancers. Mod Pathol 21(11):1371–1378

    Article  PubMed  CAS  Google Scholar 

  • Sebo TJ, Cheville JC, Riehle DL, Lohse CM, Pankratz VS, Myers RP, Blute ML, Zincke H (2002) Perineural invasion and MIB-1 positivity in addition to Gleason score are significant preoperative predictors of progression after radical retropubic prostatectomy for prostate cancer. Am J Surg Pathol 26(4):431–439

    Article  PubMed  Google Scholar 

  • Shimizu Y, Segawa T, Inoue T, Shiraishi T, Yoshida T, Toda Y, Yamada T, Kinukawa N, Terada N, Kobayashi T, Kinoshita H, Kamoto T, Nakamura E, Ogawa O (2007) Increased Akt and phosphorylated Akt expression are associated with malignant biological features of prostate cancer in Japanese men. BJU Int 100(3):685–690

    Article  PubMed  Google Scholar 

  • Siddiqui SA, Sengupta S, Slezak JM, Bergstralh EJ, Leibovich BC, Myers RP, Zincke H, Blute ML (2006) Impact of patient age at treatment on outcome following radical retropubic prostatectomy for prostate cancer. J Urol 175(3 Pt 1):952–957

    Article  PubMed  Google Scholar 

  • Signoretti S, Montironi R, Manola J, Altimari A, Tam C, Bubley G, Balk S, Thomas G, Kaplan I, Hlatky L, Hahnfeldt P, Kantoff P, Loda M (2000) Her-2-neu expression and progression toward androgen independence in human prostate cancer. J Natl Cancer Inst 92(23):1918–1925

    Article  PubMed  CAS  Google Scholar 

  • Skacel M, Ormsby AH, Pettay JD, Tsiftsakis EK, Liou LS, Klein EA, Levin HS, Zippe CD, Tubbs RR (2001) Aneusomy of chromosomes 7, 8, and 17 and amplification of HER-2/neu and epidermal growth factor receptor in Gleason score 7 prostate carcinoma: a differential fluorescent in situ hybridization study of Gleason pattern 3 and 4 using tissue microarray. Hum Pathol 32(12):1392–1397

    Article  PubMed  CAS  Google Scholar 

  • Strohmeyer D, Rossing C, Strauss F, Bauerfeind A, Kaufmann O, Loening S (2000) Tumor angiogenesis is associated with progression after radical prostatectomy in pT2/pT3 prostate cancer. Prostate 42(1):26–33

    Article  PubMed  CAS  Google Scholar 

  • Sweat SD, Pacelli A, Bergstralh EJ, Slezak JM, Cheng L, Bostwick DG (1999) Androgen receptor expression in prostate cancer lymph node metastases is predictive of outcome after surgery. J Urol 161(4):1233–1237

    Article  PubMed  CAS  Google Scholar 

  • Szende B, Romics I, Torda I, Bely M, Szegedi Z, Lovasz S (1999) Apoptosis, mitosis, p53, bcl(2), Ki-67 and clinical outcome in prostate carcinoma treated by androgen ablation. Urol Int 63(2):115–119

    Article  PubMed  CAS  Google Scholar 

  • Thomas GV, Schrage MI, Rosenfelt L, Kim JH, Salur G, deKernion JB, Dorey F, Said J, Reiter RE (2000) Preoperative prostate needle biopsy p27 correlates with subsequent radical prostatectomy p27, Gleason grade and pathological stage. J Urol 164(6):1987–1991

    Article  PubMed  CAS  Google Scholar 

  • UK NCINN (2011) Major Surgical Resections England, 2004–2006

  • Umbas R, Isaacs WB, Bringuier PP, Schaafsma HE, Karthaus HF, Oosterhof GO, Debruyne FM, Schalken JA (1994) Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer. Cancer Res 54(14):3929–3933

    PubMed  CAS  Google Scholar 

  • Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, Ghosh D, Pienta KJ, Sewalt RG, Otte AP, Rubin MA, Chinnaiyan AM (2002) The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419(6907):624–629

    Article  PubMed  CAS  Google Scholar 

  • Veltri RW, Isharwal S, Miller MC, Epstein JI, Mangold LA, Humphreys E, Partin AW (2008) Long-term assessment of prostate cancer progression free survival: evaluation of pathological parameters, nuclear shape and molecular biomarkers of pathogenesis. Prostate 68(16):1806–1815

    Article  PubMed  Google Scholar 

  • Vergis R, Corbishley CM, Norman AR, Bartlett J, Jhavar S, Borre M, Heeboll S, Horwich A, Huddart R, Khoo V, Eeles R, Cooper C, Sydes M, Dearnaley D, Parker C (2008) Intrinsic markers of tumour hypoxia and angiogenesis in localised prostate cancer and outcome of radical treatment: a retrospective analysis of two randomised radiotherapy trials and one surgical cohort study. Lancet Oncol 9(4):342–351

    Article  PubMed  Google Scholar 

  • Vergis R, Corbishley CM, Thomas K, Horwich A, Huddart R, Khoo V, Eeles R, Sydes MR, Cooper CS, Dearnaley D, Parker C (2010) Expression of Bcl-2, p53, and MDM2 in localized prostate cancer with respect to the outcome of radical radiotherapy dose escalation. Int J Radiat Oncol Biol Phys 78(1):35–41

    Article  PubMed  CAS  Google Scholar 

  • Verhagen PC, Tilanus MG, de Weger RA, van Moorselaar RJ, van den Tweel JG, Boon TA (2002) Prognostic factors in localised prostate cancer with emphasis on the application of molecular techniques. Eur Urol 41(4):363–371

    Article  PubMed  CAS  Google Scholar 

  • Vis AN, Noordzij MA, Fitoz K, Wildhagen MF, Schroder FH, van der Kwast TH (2000) Prognostic value of cell cycle proteins p27(kip1) and MIB-1, and the cell adhesion protein CD44 s in surgically treated patients with prostate cancer. J Urol 164(6):2156–2161

    Article  PubMed  CAS  Google Scholar 

  • Watanabe M, Ushijima T, Kakiuchi H, Shiraishi T, Yatani R, Shimazaki J, Kotake T, Sugimura T, Nagao M (1994) p53 gene mutations in human prostate cancers in Japan: different mutation spectra between Japan and western countries. Jpn J Cancer Res 85(9):904–910

    Article  PubMed  CAS  Google Scholar 

  • Woodson K, O’Reilly KJ, Ward DE, Walter J, Hanson J, Walk EL, Tangrea JA (2006) CD44 and PTGS2 methylation are independent prognostic markers for biochemical recurrence among prostate cancer patients with clinically localized disease. Epigenetics 1(4):183–186

    Article  PubMed  Google Scholar 

  • Wu TT, Hsu YS, Wang JS, Lee YH, Huang JK (2003) The role of p53, bcl-2 and E-cadherin expression in predicting biochemical relapse for organ confined prostate cancer in Taiwan. J Urol 170(1):78–81

    Article  PubMed  CAS  Google Scholar 

  • Wu TT, Wang JS, Jiaan BP, Yu CC, Tsai JY, Lin JT, Huang JK (2007) Role of p21(WAF1) and p27(KIP1) in predicting biochemical recurrence for organ-confined prostate adenocarcinoma. J Chin Med Assoc 70(1):11–15

    Article  PubMed  Google Scholar 

  • Yang G, Truong LD, Wheeler TM, Thompson TC (1999) Caveolin-1 expression in clinically confined human prostate cancer: a novel prognostic marker. Cancer Res 59(22):5719–5723

    PubMed  CAS  Google Scholar 

  • Yang G, Timme TL, Frolov A, Wheeler TM, Thompson TC (2005) Combined c-Myc and caveolin-1 expression in human prostate carcinoma predicts prostate carcinoma progression. Cancer 103(6):1186–1194

    Article  PubMed  CAS  Google Scholar 

  • Yoshimoto M, Cunha IW, Coudry RA, Fonseca FP, Torres CH, Soares FA, Squire JA (2007) FISH analysis of 107 prostate cancers shows that PTEN genomic deletion is associated with poor clinical outcome. Br J Cancer 97(5):678–685

    Article  PubMed  CAS  Google Scholar 

  • Yoshimoto M, Joshua AM, Cunha IW, Coudry RA, Fonseca FP, Ludkovski O, Zielenska M, Soares FA, Squire JA (2008) Absence of TMPRSS2:ERG fusions and PTEN losses in prostate cancer is associated with a favorable outcome. Mod Pathol 21(12):1451–1460

    Article  PubMed  CAS  Google Scholar 

  • Zang X, Thompson RH, Al-Ahmadie HA, Serio AM, Reuter VE, Eastham JA, Scardino PT, Sharma P, Allison JP (2007) B7–H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome. Proc Natl Acad Sci U S A 104(49):19458–19463

    Article  PubMed  CAS  Google Scholar 

  • Zellweger T, Gunther S, Zlobec I, Savic S, Sauter G, Moch H, Mattarelli G, Eichenberger T, Curschellas E, Rufenacht H, Bachmann A, Gasser TC, Mihatsch MJ, Bubendorf L (2009) Tumour growth fraction measured by immunohistochemical staining of Ki67 is an independent prognostic factor in preoperative prostate biopsies with small-volume or low-grade prostate cancer. Int J Cancer 124(9):2116–2123

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

N Kachroo is supported by the Urology Foundation Research Scholarship, a Royal College of Surgeons of England Research Fellowship and a Raymond and Beverley Sackler Studentship (University of Cambridge). This work was also supported by the Evelyn Trust, Cambridge and the Ralph Shackman Trust.

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No potential conflicts of interest to disclose.

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  1. Translational Prostate Cancer Group, Hutchison MRC Research Centre, University of Cambridge, Hills Road, Cambridge, CB2 0XZ, UK

    Naveen Kachroo & Vincent J. Gnanapragasam

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  1. Naveen Kachroo
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  2. Vincent J. Gnanapragasam
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Correspondence to Vincent J. Gnanapragasam.

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Kachroo, N., Gnanapragasam, V.J. The role of treatment modality on the utility of predictive tissue biomarkers in clinical prostate cancer: a systematic review. J Cancer Res Clin Oncol 139, 1–24 (2013). https://doi.org/10.1007/s00432-012-1351-7

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  • DOI: https://doi.org/10.1007/s00432-012-1351-7

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