前列腺干细胞抗原在人前列腺癌组织中的表达及意义

目的　探讨前列腺干细胞抗原 (PSCA)在国人前列腺癌 (PCa)组织中表达的临床意义。　方法　采用免疫组织化学 (IHC)和核酸原位杂交 (ISH)方法检测 4 0例PCa、2 0例良性前列腺增生(BPH)和 2 0例前列腺上皮内瘤 (PIN)组织标本PSCA蛋白和mRNA表达 ,半定量法计算PSCA阳性表达细胞百分数和阳性表达强度 ,比较各组织间表达水平的差异及其与PCa分级、临床分期之间的关系。　结果　PCa、BPH、PIN组织PSCA中度阳性到强阳性表达分别为 85 % (34/ 4 0 )、2 0 % (4/ 2 0 )和35 % (7/ 2 0 ) ;PCa组织PSCA表达水平与BPH和PIN比较差异有统计学意义 (P <0 .0 5 ) ,BPH与PIN比较差异无统计学意义 (P >0 .0 5 ) ;PCa组织PSCA表达水平随Gleason评分及临床分期增加而升高。　结论　人PCa组织有PSCA蛋白质和mRNA的过表达 ,且与PCa病理分级、临床分期呈正相关 ,可能对PCa的诊断及判断预后有潜在价值。     

External beam radiotherapy (EBRT) suppressed prostate stem cell antigen (PSCA) mRNA expression in clinically localized prostate cancer

BACKGROUND: Prostate stem cell antigen (PSCA), a recently identified glycosylphosphatidylinositol (GPI)-anchored cell surface protein belonging to the Thy-1/Ly-6 family of cell surface antigens, is overexpressed in human prostate cancer (PCa). Our recent data indicated that complete androgen ablation could significantly suppress PSCA mRNA expression in primarily organ-confined PCa. The effect of external beam radiotherapy (EBRT), one of the curative treatment options for localized PCa, on tumor PSCA mRNA expression has not been elucidated. The purpose of the present study was to investigate the variations in the expression levels of PSCA mRNA before and after EBRT, and further evaluate the prognostic value of PSCA in this disease. MATERIALS AND METHODS: Between January 1999 and June 2005, 87 men with clinically localized adenocarcinoma of the prostate received only EBRT with a total dose of 65-70 Gy for 6.5-7 weeks. PSCA in situ hybridization (ISH) was performed on the cancerous pretreatment biopsy or transurethral resection of prostate (TURP) tissue and post-treatment biopsy tissue of all 87 men, respectively. Tumor cytoplasmic staining of PSCA mRNA was evaluated by two independent pathologists and the differences of PSCA mRNA expression levels between the samples before and after EBRT were analyzed using the Student's t-test. Twenty-four to seventy months continuous follow-up studies after treatment were performed and aimed at assessing the correlation of PSCA mRNA expression level with biochemical relapse and/or distant metastases from the cancer. RESULTS: The percent of cells positive for PSCA mRNA by ISH labeling declined from 71.2% (0-93%) +/- 9.7% before EBRT to 30.7% (0-90%) +/- 5.3% after EBRT (P<0.001). Before EBRT, 81 of 87 cases (93.1%) were positive for PSCA mRNA labeling, however, after EBRT the percentage of positive reactivity of PSCA mRNA was decreased to 62 of 81 cases (76.5%), in which 59 men (95.2%) were found without biochemical relapse or distant metastases on follow-up. This decline in PSCA mRNA labeling was directly proportional to higher pretreatment serum PSA level, higher tumor grade (Gleason score), and higher clinical T stage. The rest 19 cases had the increased percentage of cells positive for PSCA mRNA after EBRT, in which 15 cases developed biochemical relapse and/or distant metastases from tumor on follow-up. CONCLUSIONS: We found that EBRT for PCa can significantly suppress PSCA mRNA expression and the elevated PSCA mRNA level after EBRT may be a clinically adverse predictor for tumor progression.     

前列腺癌组织中前列腺干细胞抗原的表达及其意义

目的 :探讨前列腺癌 (PCa)组织中前列腺干细胞抗原 (prostatestemcellantigen ,PSCA)的表达及其意义。方法 :应用核酸分子原位杂交 (ISH)技术 ,对 2 6例PCa和 9例正常前列腺 (NP)组织中PSCAmRNA进行检测和定位。结果 :PSCAmRNA在PCa组织表达阳性率为 84 .6 % ,其中强阳性率为 5 7.7% ;NP组织阳性率为6 6 .7% (均为弱阳性 )。PCa与NP组织表达水平差异有极显著性意义 (P <0 .0 1)。PSCAmRNA在PCa组织主要表达于癌细胞 ,细胞间质和肌肉组织均无表达 ;NP组织表达则定位于前列腺上皮的基底细胞层。PSCAmR NA表达水平与PCa临床分期、病理分级均无相关性 (P >0 .0 5 )。结论 :PSCA在探索PCa起源、PCa免疫靶向治疗方面有重要意义     

The association of prostate stem cell antigen (PSCA) mRNA expression and subsequent prostate cancer risk in men with benign prostatic hyperplasia following transurethral resection of the prostate

BACKGROUND: Prior data showed prostate stem cell antigen (PSCA) mRNA expression in benign prostatic hyperplasia (BPH) tissues. The purpose of the present investigation was to determine whether PSCA mRNA expression in resected BPH samples was associated with the subsequent presence of cancer following transurethral resection of the prostate (TURP). METHODS: PSCA in situ hybridization was performed on the TURP-resected tissues from 288 patients, who were histopathologically confirmed BPH without cancer. All these patients were continuously followed for 9-70 months postoperatively. Univariate and multivariate cox regression analyses were used to evaluate the predictive performance of PSCA mRNA for subsequent cancer onset following TURP. RESULTS: PSCA mRNA was detected in 93/288 (32.3%) of the resected BPH specimens, with a mean positive-labeling cells of 23.8%, in which 22 patients (23.7%) were identified as having PCa on follow-up. Of 195 patients with negative expression for PSCA mRNA 2 (1.0%) were subsequently found with PCa. PSCA mRNA expression levels were directly proportional to higher Gleason score and clinical T stage. Univariate and multivariate cox regression analyses demonstrated that only PSCA mRNA expression was predictive of the subsequent cancer development after TURP, however, PSA velocity was an univariately significant but not multivariately significant predictor. CONCLUSIONS: This prospective study identifies PSCA mRNA in BPH as a significant predictor of cancer development after TURP, suggesting that PSCA may be used to identify patients who are at high risk for subsequent cancer onset following TURP for BPH and the PSCA test may be useful when applied for repeat biopsies.     

Prostate stem cell antigen expression is associated with gleason score, seminal vesicle invasion and capsular invasion in prostate cancer

PURPOSE: Few successful therapeutic options exist for men who present with metastatic prostate cancer (CaP) or for the 30% with recurrence. The development and characterization of molecular markers are vital to the development of prognostic and therapeutic modalities in CaP. We investigated the expression and potential clinical usefulness of prostate stem cell antigen (PSCA) in CaP using tissue microarrays. MATERIALS AND METHODS: Immunohistochemical analysis using a PSCA monoclonal antibody was performed on tissue microarrays constructed from paraffin embedded specimens from 246 patients who underwent radical retropubic prostatectomy. PSCA staining was correlated with established prognostic factors, such as Gleason score, prostate specific antigen (PSA), and seminal vesicle invasion. In addition, recurrence-free survival was analyzed. RESULTS: A high PSCA intensity of 3 was associated with adverse prognostic features, such as Gleason score 7 and above (p = 0.001), seminal vesicle invasion (p = 0.005) and capsular involvement (p = 0.033). On univariate analysis tumors with a PSCA intensity of 3 carried an increased risk of PSA recurrence (p = 0.031, HR 1.77, 95% CI 1.05 to 2.96). However, after adjusting for these variables a PSCA intensity of 3 was no longer an independent predictor of PSA recurrence. CONCLUSIONS: We found that high PSCA intensity is significantly associated with adverse prognostic features such as high Gleason score and extra-organ disease. The results of this study suggest that PSCA is a promising tumor marker for the selection of patients at high risk but additional studies are necessary to assess the usefulness of PSCA in patient biopsies.     

Family history of prostate cancer and obesity in relation to high-grade disease and extraprostatic extension in young men with prostate cancer

BACKGROUND: Little is known about predictors of prostate cancer severity in young men. Therefore, we examined whether family history and obesity influence risk of high-grade disease and extraprostatic extension in men < 55-years old. METHODS: Four hundred ninety-eight men aged < 55 years who had had a radical prostatectomy (1992-1999) by one surgeon were mailed a survey in 2000 to assess family history of PCa and anthropometrics. Body mass index (BMI = kg/m(2)) was calculated as an indicator of obesity. Logistic regression was used to compute odds ratios (OR) for high-grade disease (Gleason score > or = 7) and extraprostatic extension. RESULTS: Of the 363 respondents, 35.8% had at least one first-degree relative with PCa. Men with a family history were younger at surgery than those without a family history (48.8 vs. 50.1 years, P < 0.001). After controlling for age, cigarette smoking, and race/ethnicity, men with an affected father had a lower risk of high-grade disease compared to those without an affected father (OR = 0.42, 95% CI 0.23-0.76). Risk of high-grade disease increased with increasing BMI, especially in men < 50-years old (P-trend = 0.02). Family history and BMI were not clearly associated with extraprostatic extension. CONCLUSIONS: After taking into account a younger age at presentation among men with a family history, young men with a family history of PCa were less likely to have high-grade disease. Obesity may be associated with a poorer histology in young men with PCa, especially in men younger than 50 years of age.     

外周血单个核细胞PSA mRNA及蛋白表达与前列腺癌微转移关系的研究

目的观察前列腺癌患者外周血单个核细胞PSA mRNA及蛋白表达,探讨其与前列腺癌微转移的关系。方法取抗凝血,Ficoll离心分离单个核细胞,RT-PCR检测PSA mRNA表达,Western blot检测PSA蛋白表达。结果(1)血清PSA>40．0ng／ml者23例,两者均表达的19例,阳性符合率82．61％(19／23);血清PSA <20．0ng／ml者16例,两者均表达的5例,阳性符合率31．25％(5／16);(2)PSA mRNA及蛋白的阳性表达与临床分期、Gleason评分均呈正相关;(3)血清PSA<20．0ng／ml的16例患者随访18个月,1例PSA mRNA及蛋白均表达阳性者,于前列腺癌根治术后半年内死于癌转移。结论外周血单个核细胞PSA mRNA及蛋白的联合检测是判断前列腺癌微转移的有效手段之一,并可预示前列腺癌的病理分级和不良预后。     

Prostate stem cell antigen (PSCA) mRNA expression in prostatic intraepithelial neoplasia: implications for the development of prostate cancer

BACKGROUND: Prior data clearly demonstrated the expression of prostate stem cell antigen (PSCA) mRNA in prostatic intraepithelial neoplasia (PIN) tissues. The purpose of the present investigation was to determine whether PSCA mRNA expression was associated with the presence of cancer in this disease. METHODS: One hundred seventeen men were diagnosed with isolated PIN on initial prostate biopsy, 51 with low-grade form (LGPIN), and 66 with high-grade form (HGPIN). PSCA mRNA expression in initial PIN and subsequent cancer was examined by in situ hybridization (ISH). The differences of the PSCA mRNA expression level between the groups were analyzed by the Chi-square and Student's t-test. Univariate and multivariate logistic regression analyses were performed to evaluate the predictive performance of PSCA mRNA. RESULTS: PSCA mRNA expression level in 34 subsequent cancers was statistically increased compared with their paired PIN (P < 0.001), with a Gleason's dependence. HGPIN showed statistically high PSCA mRNA expression compared with LGPIN (P < 0.01). PSCA mRNA expression levels were significantly stronger in the initial isolated LGPIN and isolated HGPIN with subsequent cancer than those without (P < 0.001 and P < 0.001, respectively). Multivariate logistic regression analysis demonstrated that only PSCA mRNA was predictive of the onset of subsequent cancer in patients with isolated LGPIN and in those with isolated HGPIN, respectively. CONCLUSIONS: Our data identify PSCA mRNA in initial PIN as a significant predictor of subsequent cancer, suggesting that PSCA implies in prostatic tumorigenesis and may be used to identify the patients with isolated PIN who are at high risk for cancer onset in the disease process.     

Complete androgen ablation suppresses prostate stem cell antigen (PSCA) mRNA expression in human prostate carcinoma

BACKGROUND: Prostate stem cell antigen (PSCA) is a recently identified glycosylphosphatidylinositol (GPI)-anchored cell surface protein belonging to the Thy-1/Ly-6 family of cell surface antigens. Prior data in prostate cancers indicated that PSCA is directly regulated by androgens and PSCA expression increases with high-tumor grade, advanced stage, extracapsular invasion, and androgen-independent progression. The effect of complete androgen ablation (CAA) on tumor PSCA mRNA expression has not been elucidated. The purpose of the present study was to investigate the variations in the expression levels of PSCA mRNA before and after CAA, and further evaluate the clinically prognostic value of PSCA in human prostate carcinoma. MATERIALS AND METHODS: PSCA in situ hybridization (ISH) was performed on the cancerous pretreatment biopsy or transurethral resection of prostate (TURP) tissue of 42 men with primarily organ-confined prostate cancer before CAA, and on their tumor tissue from radical retropubic prostatectomy after CAA with bicalutamide and goserelin acetate for 3 months prior to undergoing radical prostatectomy. Tumor cytoplasmic staining of PSCA mRNA was evaluated by two independent pathologists and the differences of PSCA mRNA expression levels between the samples before and after CAA were analyzed using the Student's t-test. Thirty-six to forty months follow-up studies after radical retropubic prostatectomy were performed and aimed at assessing the correlation of PSCA mRNA expression level with local recurrences or metastases from the cancer. RESULTS: The percent of cells positive for PSCA mRNA by ISH labeling declined from 67.3% (0-89%)+/-9.4% before CAA to 33.8% (0-92%)+/-7.7% after CAA (P<0.001). Before CAA, 40 of 42 cases (95.2%) were positive for PSCA mRNA labeling, however, after CAA the percentage of positive reactivity of PSCA mRNA was decreased to 27 of 40 cases (67.5%), in which none was found with local recurrences or distant metastases after radical prostatectomy on follow-up. This decline in PSCA mRNA labeling was dependent on the original tumor grade with Gleason score of or=8: 73.4%+/-13.8% (P<0.05, respectively). The rest 13 cases had the increased percentage of cells positive for PSCA mRNA after CAA, in which 3 cases were found with local recurrences and 4 cases with distant metastases from tumor on follow-up. CONCLUSIONS: Our data demonstrate that CAA for prostate cancer can suppress PSCA mRNA expression with a tumor grade dependence and the increased expression of PSCA mRNA after CAA may be a clinically adverse predictor for tumor recurrences or distant metastases.     

Epidermal growth factor receptor (ErbB1) expression in prostate cancer progression: correlation with androgen independence

BACKGROUND: The role of the epidermal growth factor receptor (ErbB1) in the progression of prostate cancer is incompletely understood. METHODS: Tissue microarrays from hormone-naive and advanced androgen-independent tumors were used to investigate the role of ErbB1 in prostate cancer progression. RESULTS: ErbB1 expression in tumor tissues was strongly associated with hormone-refractory status (odds ratio = 6.67, 95% CI = (2.6, 17.4), P = 0.0001). However, ErbB1 overexpression was not a statistically significant covariate in a multivariate proportional hazards model for biochemical failure of hormone-na?ve prostate cancer. Moreover, ErbB1 overexpression was not associated with tumor differentiation (P = 0.44), positive margins (P = 0.53), seminal vesicle invasion (P = 0.69), extraprostatic extension (P = 0.10), or preoperative PSA (P = 0.18) in the hormone-na?ve group. CONCLUSIONS: These findings are consistent with a model in which ErbB1 expression increases during the development of the androgen-independent state, and suggest that drugs targeted toward ErbB signaling could be of therapeutic relevance in the management of advanced prostatic carcinoma.     

经会阴前列腺24针饱和穿刺活检与14针活检在PSA＜20μg/L患者中筛检前列腺癌的对比性研究

目的:探讨超声引导下经会阴前列腺24针饱和穿刺活检与14针穿刺活检方案对PSA<20μg/L可疑前列腺癌患者的筛检阳性率及其相关并发症。方法:选取116例可疑前列腺癌患者行经会阴超声引导下14针穿刺活检(14针组),另136例患者,行经会阴24针饱和前列腺穿刺活检(24针饱和组),比较两组前列腺癌筛检阳性率、标本阳性率及穿刺后肉眼血尿、泌尿系感染、尿潴留等并发症的发生率。结果:两组患者平均年龄、穿刺前PSA水平、平均前列腺体积等指标均无统计学差异(P>0.05)。24针饱和组及14针组前列腺癌筛检总体阳性率分别为48.53%和17.24%,存在显著性差异(P<0.001),标本阳性率分别为8.09%和2.83%(P=0.012);其中24针饱和组前列腺尖部肿瘤的检出率(11.76%)显著高于14针组(1.72%,P<0.05)。两组穿刺后尿潴留、泌尿系感染和肉眼血尿等发生率均无统计学差异(P>0.05)。结论:24针经会阴前列腺饱和穿刺活检方法显著提高PSA<20μg/L患者中前列腺癌的筛检阳性率,尤其是增加了前列腺尖部区域的肿瘤筛检阳性率,而并未增加相关并发症。     

The diagnostic utility of novel immunohistochemical marker ERG in the workup of prostate biopsies with "atypical glands suspicious for cancer"

A diagnosis of "atypical glands suspicious for cancer" (ATYP) in prostate needle biopsy is associated with a 40% to 50% risk of finding prostate carcinoma (PCa) in subsequent biopsies. Many studies have attempted to identify clinical, histologic, or molecular characteristics of ATYP that correlated with the risk of PCa in follow-up biopsies. TMPRSS2:ERG gene rearrangement is the most common chromosomal alteration and is highly specific for PCa. Recently, 2 studies reported that positive immunohistochemical (IHC) stains with an ERG antibody highly correlated with the TMPRSS2:ERG gene rearrangement status. We evaluated the use of this antibody as an IHC marker on prostate biopsies with an initial ATYP diagnosis to determine whether positive ERG IHC was associated with increased PCa detection in subsequent biopsies, which therefore might be useful for stratifying ATYP prostate biopsies. ERG IHC was performed on 103 biopsies with initial ATYP diagnosis. Positive ERG IHC staining was detected in 16 of the 103 cases (15.5%) of the ATYP prostate biopsies. Of these 16 ERG-positive cases, the atypical glands were positive for ERG in 9 cases. In the remaining 7 cases, positive ERG staining was found in glands other than ATYP glands, including high-grade prostatic intraepithelial neoplasia and morphologically benign glands. ERG IHC was negative in other benign prostate lesions, including simple atrophy, partial atrophy, proliferative inflammatory atrophy, basal cell hyperplasia, postatrophic hyperplasia, and squamous metaplasia. In subsequent follow-up biopsies, PCa was detected in 7 of the 16 (43.8%) ERG-positive cases and in 42 of the 87 (48.3%) ERG-negative cases (P=0.952 by χ test). In biopsies with ERG-positive ATYP glands, cancer was found in 5 of 9 (55.6%) cases in subsequent biopsies. This is the first study to investigate the use of ERG IHC in difficult prostate biopsies. ERG IHC was positive in a small percentage (15.5%) of the ATYP prostate biopsies, and positive ERG staining did not correlate with the increased cancer detection in subsequent prostate biopsies. Therefore, ERG IHC is not useful for stratifying ATYP prostate biopsies to identify patients who have increased risk for PCa in repeat biopsies. Furthermore, positive ERG staining is not entirely specific for PCa and can occasionally be found in high-grade prostatic intraepithelial neoplasia and benign glands that are not associated with PCa in prostate biopsies.     

6种microRNAs在前列腺癌组织中的表达

目的:研究表明miRNAs在人类恶性肿瘤的发生发展过程中起着重要作用,本研究检测6种miRNAs:miR-98、let-7d、let-7g、miR-96、miR-182及miR-183在前列腺癌组织中的表达情况及其临床意义。方法:采用原位分子杂交方法,结合组织芯片技术分别检测38例BPH和52例前列腺癌中6种miRNAs的表达情况。并对前列腺癌组织中6种miRNA与Gleason评分,临床分期及6种miRNA间进行相关分析。结果:6种miRNAs中,与BPH组织相比,在前列腺癌组织中表达降低的为miR-98、let-7d、let-7g;而表达升高的为miR-96、miR-182及miR-183,差异均有统计学意义(P<0.05)。6种miRNAs的表达与前列腺癌的Gleason评分均相关(P<0.05),但与患者的年龄及血清PSA水平均无明显相关性(P>0.05)。其中miR-96和miR-182的表达与前列腺癌的临床分期均有相关性(P<0.05),miR-98和miR-96的表达均与肿瘤累及前列腺的叶数存在相关性(P<0.05)。另外,前列腺癌组织中,miR-96、miR-182及miR-183的表达彼此之间呈正相关(P<0.01,r分别为0.41,0.44),let-7d与let-7g的表达之间呈正相关(P<0.01,r=0.46),miR-98与let-7d及let-7g的表达之间呈正相关(P<0.05,r分别为0.31,0.34)。结论:miR-98、let-7d、let-7g、miR-96、miR-182及miR-183构成的miRNA表达谱在一定程度上反映了前列腺癌的生物学行为,可能作为前列腺癌早期诊断和预后评估的重要生物标记物。     

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。     

LC3A蛋白在前列腺癌中的表达及意义

目的:探讨LC3A蛋白在前列腺癌中的表达及意义。方法:应用免疫组化方法检测LC3A在54例前列腺癌和14例良性前列腺增生(BPH)中的表达状况。结果:LC3A蛋白阳性信号定位于细胞质和/或细胞核,在前列腺癌中胞质强阳性率为90.7%,在BPH中的胞质强阳性率为14.3%,两组差异有显著性(P0.01);并发现前列腺癌中22例核着色(40.7%),LC3A胞质表达与细胞核表达无相关性(P0.05)。LC3A表达与Gleason评分呈正相关(胞质r=0.297,P=0.029;胞核r=0.288,P=0.034)。LC3A与患者的临床分期、年龄、雄激素受体(AR)及术前患者血清PSA及结合PSA(cPSA)水平均无相关性(P0.05)。LC3A在前列腺癌及BPH组织间质中的纤维细胞及平滑肌细胞也见着色。AR在前列腺癌中阳性率为74.1%(40/54),在BPH的阳性率为64.3%(9/14)。两者阳性率差异无统计学意义。结论:LC3A可能与前列腺癌的发生、分化及预后有关。     

Metastasis suppressor gene Raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancer

BACKGROUND: Diminished expression of Raf kinase inhibitor protein (RKIP), an inhibitor of the Raf signaling cascade, promotes prostate cancer (PCa) metastasis in a murine model, suggesting that it is a metastasis suppressor gene. However, the prognostic significance of RKIP expression and its association with metastasis in PCa patients is unknown. METHODS: To investigate RKIP protein expression is a prognostic marker in PCa we performed immunohistochemical staining for RKIP expression in tissue microarrays consisting of 758 non-neoplastic prostate tissues, primary tumors and metastases from 134 PCa patients. The Cox proportional-hazards model was used to adjust for covariates including Gleason score, tumor volume, tumor weight, clinical stage, digital rectal exam findings, serum PSA level and surgical margins. RESULTS: RKIP expression was low in approximately 5%, 48%, and 89% of non-neoplastic prostate, primary tumors and metastases, respectively. Low RKIP expression in primary tumors was a strong positive predictive factor for PCa recurrence based on PSA levels. In patients whose primary tumors expressed high RKIP levels, the 7-year PSA recurrence rate was <10%; whereas in patients with tumors with low RKIP expression the recurrence rate was 50% (P<0.001). Multivariate analysis revealed RKIP was an independent prognostic factor (P<0.001). CONCLUSION: In contrast to increased expression of pro-tumorigenic genes, these results demonstrate decreased protein expression of a gene, for example, RKIP, can serve as a prognostic marker in PCa patients.