The value of EZH2, p27kip1, BMI‐1 and MIB‐1 on biopsy specimens with low‐risk prostate cancer in selecting men with significant prostate cancer at prostatectomy

OBJECTIVE

To assess the additional prognostic value of the molecular markers EZH2, MIB‐1, p27^kip1 and BMI‐1 on needle biopsies from men with low‐risk prostate cancer, as this disease in needle biopsies shows a heterogeneous clinical outcome, and while it is known that the expression of these tissue markers is predictive of the clinical outcome after radical prostatectomy (RP) their value in prostate biopsies is largely unknown.

PATIENTS AND METHODS

The study included men participating in a screening study, diagnosed with low‐risk prostate cancer and subsequently treated with RP. Immunohistochemical staining for EZH2, MIB‐1, p27^kip1 and BMI‐1 on the needle biopsies were (semi)quantitatively scored and expression levels were related to significant disease at RP. Clinical low‐risk prostate cancer was defined as a prostate‐specific antigen (PSA) level of ≤10 ng/mL, clinical T‐stage ≤2, biopsy Gleason score ≤6, a PSA density of <0.20 ng/mL/g and two or fewer positive cores. Significant PC at RP was defined as presence of any of extracapsular extension, Gleason pattern 4/5, or tumour volume ≥0.5 mL.

RESULTS

In all, 86 biopsy specimens were included; there was high EZH2 expression (>1.0%) in 42% and a low p27^kip expression (<90%) in 63%. Significant disease was present in 44 (51%) RP specimens. A high EZH2 (odds ratio 3.19, P = 0.043) and a low p27^kip1 (4.69, P = 0.036) were independent predictors for significant prostate cancer at RP.

CONCLUSIONS

The determination of EZH2 and p27^kip1 on diagnostic needle biopsies supports the selection of men with indolent prostate cancer at RP. Especially p27^kip1 could improve the pretreatment risk assessment of patients with low‐risk prostate cancer.     

Caveolin-1 overexpression is associated with aggressive prostate cancer recurrence

BACKGROUND: Caveolin-1 protein suppresses apoptotic cell death in prostate cancer. The objectives of this study were to investigate the association of Caveolin-1 expression with established features of prostate cancer as well as overall and aggressive disease recurrence in patients treated with radical prostatectomy (RP). METHODS: Caveolin-1 immunostaining was performed on a tissue microarray containing prostatectomy specimen cores from 232 consecutive patients treated with RP for clinically localized prostatic adenocarcinoma. Caveolin-1 over-expression was defined as more than 50% of cells staining positively for Caveolin-1. Patients were categorized as having features of aggressive disease recurrence if they had a positive metastatic work-up, post-recurrence PSA doubling time less than 10 months, and/or failure to respond to local salvage radiation therapy. RESULTS: Seventy patients (30.2%) exhibited over-expression of Caveolin-1. Caveolin-1 over-expression was associated with higher pathologic Gleason sum (P=0.038) and higher pre-operative PSA level (P=0.024). Patients with Caveolin-1 over-expression were at increased risk of PSA recurrence after surgery (P=0.023) in univariate but not in standard post-operative multivariate analysis. However, patients with Caveolin-1 over-expression were at increased risk of aggressive prostate cancer recurrence in both univariate and multivariate analysis (P<0.001 and P=0.001, respectively). CONCLUSIONS: Over-expression of Caveolin-1 was associated with established features of prostate cancer and aggressive PSA recurrence. Caveolin-1 might help identify patients at high risk of developing aggressive prostate cancer recurrence, thus allowing selection of patients who might benefit from early systemic therapeutic intervention.     

ERG蛋白表达与前列腺癌患者根治术后生化复发风险关系的研究

目的 探讨临床局限性前列腺癌行根治性切除术后,组织ERG蛋白表达情况与术后生化复发的相关性。方法 选取2012年3月至2016年2月在本院治疗的121例局限性前列腺癌并行根治性切除术的患者作为研究对象,通过住院病历及门诊随访资料收集患者确诊时年龄、血清前列腺特异性抗原（PSA）水平、格里森评分（GS）、病理分期及切缘状态等参数。结果 共有98例患者完成最终随访,ERG蛋白表达阳性率为35.7%（35/98）。Kaplan-meier生存分析提示,确诊时PSA水平（P=0.007）、GS（P=0.024）及ERG蛋白表达状态（P<0.0001）,与术后生化复发相关。Cox回归多因素分析显示,确诊时PSA水平（HR=2.134,P=0.001）、GS（HR=1.361,P=0.030）及ERG蛋白表达状态(HR=2.024,P=0.044)分别为前列腺癌根治性切除术后生化复发的独立危险因素。结论 ERG蛋白表达状态是前列腺根治性切除术后生化复发的独立危险因素,通过对其检测及分析,可以为患者制定个体化的随访及临床治疗方案提供参考依据。     

Prognostic significance of primary Gleason pattern in Japanese men with Gleason score 7 prostate cancer treated with radical prostatectomy

ObjectivesTo evaluate the significance of the primary Gleason pattern in patients with Gleason score (GS) 7 prostate cancer treated with radical prostatectomy.Materials and methodsThis study included 959 consecutive Japanese men who underwent radical prostatectomy without neoadjuvant therapies and were subsequently diagnosed as having GS 7 prostate cancer based on the modified International Society of Urological Pathology (ISUP) 2005 Gleason grading system.ResultsOf these 959 patients, 666 (69.4%) and 293 (30.6%) had GS 3+4 and GS 4+3 tumors, respectively. There were significant differences in the prostate-specific antigen (PSA) level, biopsy GS, pathologic T stage, lymphatic invasion, microvenous invasion, and perineural invasion between these 2 groups. During the mean observation of 48.9 months, biochemical recurrence occurred in 211 patients (22.0%), and there was a significant difference in the biochemical recurrence-free survival between patients with GS 3+4 tumors and those with GS 4+3 tumors. Of several factors examined, biochemical recurrence-free survival was significantly associated with the PSA level, biopsy Gleason score, capsular penetration, seminal vesicle invasion, surgical margin status, lymphatic invasion, microvenous invasion, perineural invasion, and primary Gleason pattern, among which the PSA level, capsular penetration, seminal vesicle invasion, and surgical margin status, but not primary Gleason pattern, appeared to be independent predictors of biochemical recurrence.ConclusionsDespite the lack of an independent significance, primary Gleason pattern based on the modified ISUP 2005 Gleason grading system is shown to be significantly associated with the biochemical outcome of Japanese men with GS 7 prostate cancer.     

Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score

OBJECTIVE: To investigate the expression and potential clinical usefulness of structure-specific flap endonuclease 1 (FEN-1) in human primary prostate cancer using tissue microarray technology, as FEN-1 was recently identified to be overexpressed in CL1.1, the most aggressive clone generated from the hormone-refractory prostate cancer cell line CL1. MATERIALS AND METHODS: Immunohistochemistry was performed on tissue microarrays constructed from paraffin-embedded specimens of primary prostate cancer from 246 patients who had had a radical prostatectomy. Prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH) and normal prostate epithelium were represented on the array. FEN-1 nuclear expression was scored based on the percentage of target cells staining positively, and correlated with Gleason score, preoperative prostate-specific antigen (PSA) level and pathological stage. The time to PSA recurrence was also analysed. RESULTS: The mean expression of FEN-1 was significantly higher in cancer (36.7%) than in normal (13.2%), BPH (4.5%) and PIN (15.4%) specimens (P < 0.001). FEN-1 expression was significantly correlated with Gleason score (ó = 0.23, P = 0.002). A higher preoperative serum PSA level (P = 0.015), Gleason score > or = 7 (P < 0.001), seminal vesicle invasion (P < 0.001) and capsular involvement (P = 0.004) were associated with PSA recurrence, whereas FEN-1 expression was not. In a multivariate analysis, only Gleason score > or = 7 (P < 0.001), seminal vesicle invasion (P = 0.005) and capsular involvement (P = 0.009) were retained as independent predictors for PSA recurrence. CONCLUSIONS: FEN-1 is overexpressed in prostate cancer compared with matched normal prostate, and its expression increases with tumour dedifferentiation, as shown by increasing Gleason score. These results suggest that FEN-1 might be a potential marker for selecting patients at high risk, and a potential target for prostate cancer diagnosis and therapy.     

前列腺特异抗原联合分级对前列腺癌患者分期的预测

目的探讨血清前列腺特异抗原(PSA)联合分级对前列腺癌患者的分期进行预测的方法。方法回顾分析我院泌尿外科187例穿刺活检诊断为前列腺癌患者的临床资料。采用等级相关分析、秩和检验、逐步判别多因素分析方法,分析血清PSA水平、游离PSA百分比(FPSA/TPSA值)与Gleason评分(GS)、分期的关系。结果前列腺癌患者GS越高,血清PSA水平越高(r=0.369,P<0.001)。分期越晚,血清PSA、GS越高(r=0.398,0.530,P均<0.001)。FPSA/TPSA值与分期不相关(P>0.70),但当PSA≤10μg/L时,FPSA/TPSA值与分期呈负相关(r=-0.600,P<0.05)。当PSA>20μg/L时,67%~87%的患者可能为C或D期。用PSA、GS预测分期的公式为x=-3.488+0.041×PSA+0.428×GS。结论血清PSA水平与GS呈正相关。血清PSA水平、GS分别与分期呈正相关。当PSA≤10μg/L时,FPSA/TPSA值与分期呈负相关。运用判别公式x=-3.488+0.041×PSA+0.428×GS可以预测前列腺癌患者的分期。     

Disease recurrence in black and white men undergoing radical prostatectomy for clinical stage T1-T2 prostate cancer

PURPOSE: The reported incidence and mortality of prostate cancer are higher among black than white men. Reasons for the disproportionate racial incidence of this disease are not known but most surveys suggest that increased mortality among black men is due to more advanced tumor stage at diagnosis. To determine if racial differences exist in men with similar stage disease we compared disease recurrence in black and white men who underwent radical prostatectomy for clinical stage T1-T2 prostate cancer. MATERIALS AND METHODS: We reviewed the records of all 257 white and 218 black men undergoing radical prostatectomy for clinical stage T1-T2 prostate cancer at the Louisiana State University Medical Center-Shreveport and the Overton-Brooks Veterans Affairs Medical Center between January 1990 and November 1998. Age, race, serum prostate specific antigen (PSA), ultrasound measured prostate volume, PSA density (PSA divided by prostate volume), histological features of the prostate biopsy, clinical stage, pathological stage, histological features of the radical prostatectomy specimen and disease recurrence were reviewed. RESULTS: Black men had significantly higher mean serum PSA and PSA density than white men (2-sided p = 0.005 and 0.03, respectively). There were no statistically significant differences by race in terms of patient age, prostate volume, clinical stage, biopsy Gleason score, pathological stage, positive pelvic lymph nodes, positive surgical margins or PSA recurrence rates. CONCLUSIONS: Black men with clinical stage T1-T2 prostate cancer who underwent radical prostatectomy had significantly higher serum PSA and PSA density than similarly treated white men. However, race appears to have no independent impact on pathological findings or disease recurrence in men with clinically localized prostate cancer treated with radical prostatectomy when the effects of differences in serum PSA are controlled.     

The Polycomb Group protein EZH2 regulates actin polymerization in human prostate cancer cells

BACKGROUND: The Polycomb Group protein EZH2 is implicated in prostate cancer progression. EZH2 promotes prostate cancer cell proliferation and invasiveness. We describe a link between EZH2 function and actin polymerization in prostate cancer cells. METHODS: Nuclear and cytoplasmic EZH2 expression in benign and malignant prostate tissue samples was assessed. An association between EZH2 function and actin polymerization in prostate cancer cells was investigated using siRNA-mediated knock-down of EZH2. Effects of EZH2 knock-down on actin polymerization dynamics were analyzed biochemically using immunoblot analysis of cell lysate fractions, and morphologically using immunocytochemistry. RESULTS: Cytoplasmic EZH2 is expressed at low levels in benign prostate epithelial cells and over-expressed in prostate cancer cells. Cytoplasmic EZH2 expression levels correlate with nuclear EZH2 expression in prostate cancer samples. Knock-down of EZH2 in PC3 prostate cancer cells increases the amount of F-actin polymerization, cell size, and formation of actin-rich filaments. CONCLUSIONS: Cytoplasmic EZH2 is over-expressed in prostate cancer cells. EZH2 function promotes a reduction in the pool of insoluble F-actin in invasive prostate cancer cells. EZH2 may regulate actin polymerization dynamics and thereby promote prostate cancer cell motility and invasiveness.     

Clinical stage T1c prostate cancer: pathologic outcomes following radical prostatectomy in black and white men

BACKGROUND: The incidence of prostate cancer in black men is 50% to 70% higher than among age-matched white men. Black men have a twofold higher mortality rate and overall tend to have higher serum prostate-specific antigen (PSA) levels than white men. To determine whether racial differences exist in men whose prostate cancer was diagnosed based solely on an elevated serum PSA level, we compared clinical and pathologic features in black and white men undergoing radical prostatectomy (RP) for clinical stage T1c prostate cancer. METHODS: We used a prospectively collected database to identify all men undergoing RP for clinical T1c prostate cancer between July 1995 and October 2000. A total of 129 consecutive men (56 black men and 73 white men) were compared for age at diagnosis, serum PSA level, biopsy Gleason score, pathologic stage, RP specimen Gleason score, incidence of lymph node metastasis, and incidence of positive surgical margins. RESULTS: Statistically significant differences were not found by race in patients' ages, serum PSA levels, biopsy Gleason score, pathologic stage, incidence of lymph node metastases, or incidence of positive surgical margins. The RP specimen Gleason score was more heterogeneous in black men than white men (P=0.02). CONCLUSIONS: Racial differences in the incidence and mortality rate of prostate cancer are well known, but differences in the clinical and pathologic features between black and white men with prostate cancer identified solely based on an elevated serum PSA level with negative results on digital rectal examination (clinical stage T1c ) have been poorly studied. Our results suggest that men with clinical stage T1c prostate cancer have similar clinical and pathologic findings regardless of race. These results suggest that early-detection programs using serum PSA testing for prostate cancer in black men potentially can result in improvements in prostate cancer outcomes in this high-risk group.     

前列腺癌组织中蛋白表达与内分泌治疗后进展的相关性研究

目的 探讨前列腺癌内分泌治疗前癌组织中多种蛋白标记表达与内分泌治疗后发生进展的相关性,筛选内分泌治疗后进展的预测因子.方法 收集116例接受内分泌治疗的前列腺癌患者的临床病理资料,检测患者内分泌治疗前癌组织中雄激素受体(AR)、上皮型钙黏附索(E-cad-herin)、嗜铬粒蛋白A(CgA)、核增殖抗原(Ki67)、凋亡抑制蛋白(Survivin)、EZH2、hepsin蛋白表达,应用Cox比例风险模型进行多因素分析.结果 Ki67、EZH2、Survivin 3种蛋白表达与传统临床病理学因素存在Spearman等级相关.单因素分析中发现临床分期(P<0.001)、Gleason评分(P=0.005)、治疗前血清PSA值(P<0.001)以及Ki67(P=0.032)、Survivin蛋白(P=0.002)表达与内分泌治疗后的进展相关,多因素分析结果 显示临床分期(T_x N_+/M_+)(P<0.001)、高病理分级(Gleason评分≥8分)(P-0.038)和Survivin蛋白高表达(p＝0.031)是内分泌治疗后进展的重要危险因素.其中T_x N_+/M_+者67例(57.8%),Gleason评分≥8分者56例(48.3%),Survivin蛋白高表达者91例(78.4%). 结论 临床分期、病理分级、Survivin蛋白表达对于预测前列腺癌内分泌治疗后进展有重要意义.     

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

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.     

Common Variants in IGF1 Pathway Genes and Clinical Outcomes After Radical Prostatectomy

Background

Insulin-like growth factor-1 (IGF1) pathway plays a critical role in malignant transformation, and epidemiology studies have also shown that single nucleotide polymorphisms (SNPs) in IGF1 pathway genes are associated with prostate cancer risk. However, the clinical significance of these SNPs on prostate cancer aggressiveness and prognosis after radical prostatectomy (RP) has not been determined.

Methods

We evaluated the associations of 4 common SNPs in IGF1 and IGF1R with age at diagnosis, preoperative prostate-specific antigen (PSA) level, pathologic Gleason score, pathologic stage, surgical margin, lymph node metastasis, and PSA recurrence in a cohort of 320 localized prostate cancer patients receiving RP. The prognostic significance on time to PSA recurrence was also assessed by Cox proportional hazards model.

Results

IGF1 rs2946834 alleles/genotypes and an IGF1 specific haplotype AT, containing the minor allele of rs2946834, were associated (P ≤ 0.028) with a 1.49- to 2.22-fold higher risk of having advanced-stage prostate cancer. In addition, a genetic interaction profile consisting of IGF1 rs2946834 and IGF1R rs2016347 was significantly associated with PSA recurrence (P = 0.033).

Conclusions

Our study is the first to evaluate the impact of SNPs in IGF1 pathway genes on PSA recurrence. A genetic interaction between IGF1 rs2946834 and IGF1R rs2016347 might be a predictor of outcomes following RP.     

Radical prostatectomy as treatment for prostate-specific antigen-detected stage T1c prostate cancer

The use of serum prostate-specific antigen (PSA) measurement as a method for early detection of prostate cancer has increased the detection of clinically and pathologically localized prostate cancer. Clinical stage T1c was introduced to describe cancers discovered on prostate biopsy as a result of an abnormal serum PSA level without a palpable prostatic abnormality on digital rectal examination. The majority of men with stage T1c tumors have significant disease warranting treatment. We report the results of anatomic radical retropubic prostatectomy as therapy for PSA-detected stage T1c prostate cancer in 340 men treated at a single institution. In all, 17 men (5%) have had a recurrence with 2.3 ± 1.2 years of follow-up, 15 of whom have experienced an isolated biochemical PSA recurrence only. The overall actuarial biochemical PSA recurrence-free rate at 6 years is 87%, with pathologic stage being the best single indicator of the likelihood of progression. Although a longer period of follow-up is needed, this interim report suggests that these men can be cured by surgery at rates equal to or better than those of previously reported radical prostatectomy series.Funding was provided by National Cancer Institute SPORE grant CA 58236     

Obesity, serum prostate specific antigen and prostate size: implications for prostate cancer detection

PURPOSE: Obesity has been associated with lower serum testosterone, theoretically resulting in decreased PSA production. Obesity has also been associated with prostatic enlargement, making the detection of existent cancer more difficult. Together these findings would result in an apparent protective effect of obesity on prostate cancer risk due to technical detection issues unrelated to cancer biology. We examined the association between BMI, and PSA and prostate weight in a cohort of men undergoing RP. MATERIALS AND METHODS: We evaluated the association of BMI with prostate weight and PSA using linear regression, adjusting for patient age at RP, year of RP, race, and pathological stage and grade in 1,414 men treated with RP between 1988 and 2004 at the 5 equal access medical centers that comprise the Shared Equal Access Regional Cancer Hospital Database. RESULTS: On multivariate analysis increasing BMI was associated with increasing prostate weight but only in men younger than 63 years and not in men 63 years or older (p-trend <0.001 and 0.44, respectively). In men younger than 63 years mean multivariate adjusted prostate weight +/- SE in those with a BMI of less than 25 vs 30 to 34.9 kg/m was 33.8 +/- 1.4 vs 41.4 +/- 1.6 gm. There was no significant association between BMI and preoperative PSA (p-trend = 0.70). CONCLUSIONS: In a cohort of men undergoing RP obesity was associated with larger prostate size but only in younger men. There was no association between BMI and PSA. Assuming equal PSA, the degree of prostatic enlargement observed in younger obese men in this study would be expected to result in a modest decrease in the odds of detecting prostate cancer in a contemporary series of PSA screened men due to the decreased sensitivity of cancer detection related to larger prostate size. Obesity may appear protective for prostate cancer in younger men due to technical issues unrelated to cancer biology.     

PIM-1在前列腺癌组织中的表达及其与PSA的关系

目的:探讨PIM-1蛋白在前列腺癌组织中的表达及其与PSA复发之间的关系。方法:利用免疫组化SP检测68例前列腺癌和37例良性前列腺增生(BPH)组织中PIM-1蛋白的表达。结果:在前列腺癌组织中PIM-1蛋白表达的阳性率为67.65%(46/68);BPH组织中40.54%(15/37),两组表达的差异有显著意义(P<0.05)。PIM-1蛋白表达的阳性率在前列腺癌Gleason分级中6分33.33%(7/21),7分75%(21/28),8～10分94.74%(18/19),组间比较差异有显著性(P<0.05)。临床分期中在Ⅰ、Ⅱ、Ⅲ、Ⅳ期PIM-1蛋白表达率分别为47.62%、53.85%、73.33%、94.74%,36个月随访PSA复发状况采用Kaplan-Meier方法分析,PIM-1蛋白表达与有无复发分别是78.26%(36/46)和45.45%(10/22),差异有显著性(P<0.05)。结论:前列腺癌中PIM-1蛋白表达与前列腺癌的Gleason分级、临床分期以及PSA复发有密切关系,提示PIM-1基因在前列腺癌演化和进展中有重要作用,可能是前列腺癌的预后指标。     

Immunohistochemical localization of human kallikreins 6, 10 and 13 in benign and malignant prostatic tissues

Human kallikreins 6, 10 and 13 (hK6, hK10 and hK13) are expressed by many normal, mainly glandular tissues, including prostatic epithelium. Some kallikreins may function as tumor suppressors or are downregulated during cancer progression. The aim of this study was to evaluate the immunoexpression of these kallikreins in benign and malignant prostatic tissues and correlate their expression with prostate cancer (PC) prognosis. Included in the study were 25 cases of nonmalignant prostate and 179 cases of PC. Among them, 122 PC cases were immunostained for hK6, 94 for hK10 and 113 for hK13, respectively. The follow-up period for a subset of 68 patients who had undergone radical prostatectomy (RP) was 1-58 months (mean=13.4 +/- 1.7 and median=8.0 months). A cutoff value of 0.2 microg/l of serum PSA was established as a biochemical recurrence threshold. Follow-up information was available for 26/55 RP cases stained for hK6, 14/32 cases stained for hK10 and 25/59 cases stained for hK13. Gleason score (GS) 7 carcinomas were stratified as 7a and 7b, according to the primary grade. PC with GS 2-7a were histologically categorized as low malignant (LM) and PC with GS 7b-10 as high malignant (HM). The immunohistochemical method of streptavidin-biotin-peroxidase using monoclonal and polyclonal antibodies was performed. In the benign prostate and in prostatic intraepithelial neoplasia, a cytoplasmic immunostaining of varying intensity was evident. In PC, the immunoexpression of all kallikreins was decreased: 102/122 cases (84%) were positive for hK6, 73/94 (78%) for hK10 and 97/113 (86%) for hK13, respectively. A statistically significant difference in expression was found, in comparison to nonmalignant prostates (P=0.029, 0.009 and 0.045, respectively). Also, a positive correlation was observed between the immunoexpression of these three kallikreins. Concerning the histological grade, HM-PC expressed all three kallikreins with a slightly higher percentage than LM-PC: 79 vs 88% for hK6, 76 vs 79% for hK10 and 76 vs 92% for hK13. These differences were statistically significant only in the case of hK13 (P=0.024). Serum PSA did not correlate with kallikrein immunoexpression in PC. Furthermore, there was no significant correlation between kallikrein expression and pathological stage or recurrence, in the cases of RP. All three kallikreins are expressed in the nonmalignant and malignant prostate, with cancer tissues demonstrating slightly lower expression. Expression levels did not correlate with aggressiveness and they do not seem to have value for prostate cancer prognosis.