Histopathological variables and biomarkers enhancer of zeste homologue 2, Ki-67 and minichromosome maintenance protein 7 as prognosticators in primarily endocrine-treated prostate cancer

Teemu T. Tolonen, Teuvo L J Tammela, Paula M. Kujala, Vilppu J. Tuominen, Jorma J. Isola, Tapio Visakorpi, Tarja Heino-Tolonen

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16 Citations (Scopus)

Abstract

OBJECTIVE To evaluate the prognostic value of histopathological variables and immunostainings of biomarkers enhancer of zeste homologue 2 (EZH2), Ki-67 and minichromosome maintenance protein 7 (MCM7) from core biopsies of hormonally treated patients with prostate cancer. PATIENTS AND METHODS Biopsies of 247 primarily endocrine-treated patients were analysed for histopathological characteristics and Gleason scores (GS) according to the revised guidelines of International Society of Urologic Pathology (ISUP) consensus conference 2005. Immunohistochemical stainings were analysed with the aid of digital image analysis. The prognostic value of the histopathological variables and the biomarkers was analysed with univariate and multivariate Cox regression analysis, with biochemical recurrence as an endpoint. RESULTS Biomarkers EZH2 (relative risk [RR] 2.0, 95% confidence interval 1.2-3.3), Ki-67 (3.4, 2.1-5.5) and MCM7 (2.4, 1.5-3.9) were significantly associated with progression-free survival in a univariate analysis. Ki-67 immunostaining index detected high-risk patients with GS of 7 (9.1, 8.0-10.3). In a multivariate analysis with non-conventional GS groups 5-7 (3 + 4), 7(4 + 3)-8, and 9-10, the independent prognostic markers were pretreatment GS (2.2, 1.5-3.2), prostate-specific antigen (PSA) level (2.1, 1.1-4.2), perineural invasion (PNI) (1.6, 1.2-2.2), and clinical T-stage (cT) (1.9, 1.0-3.7). Combination of the independent markers (PSA level >20 ng/mL or GS >3 + 4 or PNI >3 or cT >2) yielded best risk stratification (RR 11.6, 10.4-12.7). CONCLUSIONs GS remains one of the most important prognostic factors in prostate cancer. However, the refined guidelines by ISUP 2005 might have shifted the threshold between low-grade and high-grade cancers from GS 6 vs 7 to GS 3 + 4 vs 4 + 3. PNI is an independent prognostic marker superior to cT. Ki-67 is the most useful biomarker in detecting patients with GS = 7 at high risk for progression.

Original languageEnglish
Pages (from-to)1430-1438
Number of pages9
JournalBritish Journal of Urology International
Volume108
Issue number9
DOIs
Publication statusPublished - 2011
Publication typeA1 Journal article-refereed

Keywords

  • Gleason score
  • ISUP 2005
  • Ki-67
  • androgen deprivation
  • perineural invasion
  • prostate cancer

Publication forum classification

  • No publication forum level

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