Prostate cancer grading: the effect of stratification of needle biopsy Gleason Score 4 + 3 as high or intermediate grade.
ABSTRACT To assess the discrepancy between needle biopsy (NB) and radical prostatectomy (RP) Gleason score (GS) in Irish men, specifically the influence of the stratification of GS 4 + 3 on overall levels of agreement, levels of discrepancy and kappa coefficients, as the GS assigned to prostate cancer NBs affects clinical decision-making and influences future therapeutic strategies.
We reviewed retrospectively a database of the discrepancies between NB and RP Gleason grades (GG) from 2003 to 2008. All patients had clinically localized prostate cancer, and none had had neoadjuvant therapy. Grading of 206 NB specimens was compared with their corresponding RP specimens. The discrepancy rate between NB and RP GS was assessed for each combination of GG. Intermediate- (GS 7, defined as GS 3 + 4 alone vs GS 7) and high-grade (GS 4 + 3 and GS 8-10 vs GS 8-10) classifications were compared. The level of agreement and the kappa coefficient for each system was assessed.
In NB, GS 6 was most frequently diagnosed (53%); after RP, GS 3 + 4 was most frequent (36%). In 42% of cases the exact GG remained unchanged after RP, increasing to 48% for GS 6 and GS 3 + 4. Overall 42% of cases showed an increase in their GG. In GS 6 NBs, the rate of increase in the primary GG or increase in the GS was 52%. Biopsy GS 6 and 3 + 4 showed the highest levels of agreement between NB and RP. Low-grade prostate cancer on NB was upgraded in 52% of cases; high-grade prostatic adenocarcinoma was downgraded in 27-77% of cases depending on the grading system used.
Classification of high-grade prostate cancer as GS 4 + 3 and GS 8-10 results in higher levels of agreement between NB and RP GS. Reliable identification of well differentiated prostatic adenocarcinoma in NB specimens represents an ongoing diagnostic challenge, necessitating careful preoperative consideration of the definitive grade of a patient's disease.
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ABSTRACT: • 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. • 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. • 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). • 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.BJU International 05/2011; 108(9):1430-8. · 3.05 Impact Factor
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ABSTRACT: Prostate carcinoma (PCa) with Gleason score (GS) 7 has to be examined differentially regarding its prognosis. Using the criteria of ISUP and supplementations, we attempted to analyze the heterogeneity of PCa with GS 7 of biopsy and corresponding specimens of radical prostatectomies (RP). PCa of 530 patients were graded according to Gleason under additional consideration of the state of the nucleoli. Investigating the biopsy specimens, we determined the pattern of Gleason 4 of GS 7, the extension of the tumors in percent, and the number of biopsies containing tumor. In the corresponding specimens of RP, the grading and the state of TNM with margins were assessed. Carcinomas with GS 7 (4+3) in biopsy and RP specimens were unequivocally assigned to the group of high-grade tumors. Carcinomas with GS 7 (3+4) were significantly different from carcinomas with GS 6 when only few and small nucleoli in GS 6 were present (low grade type, p≤0.0001), but were similar to the GS 6 group when nucleoli were prominent (intermediary type, p=0.71). The intermediary group showed an upgrading rate of 36% from GS 6 to GS 7. Furthermore the correlation between organ-confined and non-organ-confined growth showed differences of 63% and 37% in the intermediary group (p=0.0001). The values of grading, staging, margins and metastases indicate that carcinomas of the prostate with the Gleason 3+4 pattern correspond to an intermediary group of carcinomas in contrast to high-grade (high risk) carcinomas with GS 7 and pattern 4+3.Pathology - Research and Practice 03/2013; 209(3):190-4. · 1.21 Impact Factor
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ABSTRACT: Background:Emerging evidence suggests that diabetes may increase the risk of cancers. However, available evidence on prostate cancer is conflicting. We therefore examined the association between Type 2 diabetes and risk of prostate cancer by conducting a detailed meta-analysis of all studies published regarding this subject.Methods:PubMed database and bibliographies of retrieved articles were searched for epidemiological studies (published between 1970 and 2011), investigating the relationship between Type 2 diabetes and prostate cancer. Pooled risk ratio (RR) was calculated using random-effects model. Subgroup, sensitivity analysis and cumulative meta-analysis were also done.Results:Forty-five studies (29 cohort and 16 case-control studies) involving 8.1 million participants and 132 331 prostate cancer cases detected a significant inverse association between Type 2 diabetes and risk of prostate cancer (RR 0.86, 95% confidence interval (CI) 0.80-0.92). For cohort studies alone, the RR was 0.87 (95% CI 0.80-0.94), and for case-control studies alone, the RR was 0.85 (95% CI 0.74-0.96). Sensitivity analysis done by excluding one outlier further strengthened our negative association (RR 0.83, 95% CI 0.78-0.87). No evidence of publication bias was observed.Conclusions:This meta-analysis provides strongest evidence supporting that Type 2 diabetes is significantly inversely associated with risk of developing prostate cancer.Prostate Cancer and Prostatic Disease advance online publication, 2 October 2012; doi:10.1038/pcan.2012.40.Prostate cancer and prostatic diseases 10/2012; · 2.10 Impact Factor