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Histopathological variables and biomarkers enhancer of zeste homologue 2, Ki‐67 and minichromosome maintenance protein 7 as prognosticators in primarily endocrine‐treated prostate cancer
Author(s) -
Tolonen Teemu T.,
Tammela Teuvo L.J.,
Kujala Paula M.,
Tuominen Vilppu J.,
Isola Jorma J.,
Visakorpi Tapio
Publication year - 2011
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2011.10253.x
Subject(s) - perineural invasion , prostate cancer , medicine , oncology , univariate analysis , concordance , cancer , pathology , multivariate analysis
Study Type – Prognosis (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Gleason score is a strong prognostic factor, but its reproducibility is not optimal. Our data show that multipte perineural invasion and Ki‐67 index are signs of early biochemical progression in patients treated with hormonal therapy. 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.