High-grade Prostatic Intraepithelial Neoplasia Patients Research Articles

Statin use linked with a decrease in the conversion from high-grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer.

The roles of obesity, metabolic dysregulation and systemic inflammation to advance prostate carcinogenesis are unclear. This study investigates metabolic and inflammatory factors in the transition from high-grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer (PC). We prospectively followed 160 men diagnosed with HGPIN at biopsy and therefore at high-risk and clinically monitored for PC. Analyses investigated body mass index (BMI), waist circumference, waist-hip ratio (WHR), height, fat mass, lean mass percent body fat, NSAIDs, statins, metformin, diabetes, hypertension, hypercholesterolemia representing metabolic dysregulation on the risk of a PC diagnosis during follow-up. Systemic inflammation was estimated through measurement of 13 plasma cytokine levels. Statin use was significantly linked with overall PC at follow-up [odds ratio (OR) = 0.45, (0.23, 0.91), P = 0.03], with a somewhat stronger link with high-grade [OR = 0.39, (0.15, 1.04), P = 0.06] PC compared with low-grade PC [OR = 0.50, (0.23, 1.12), P = 0.09]. Non-statin cholesterol-lowering medications, BMI, WHR, diabetes, hypertension and percent body fat were not significantly associated with PC. Although blood IL-12p70, IL-2 and IL-1β levels were significantly lower among statin users, inflammatory markers were not significantly linked with PC and did not explain the observed relationship between statins and lower PC risk. In summary, this prospective study of HGPIN patients at high risk for PC finds that statin use was significantly associated with reduced risk of PC detection at follow-up. Systemic markers of inflammation did not mediate this association, suggesting that statins affect PC progression through alternative pathways.

Outcomes of Prostate Atypical Small Acinar Proliferation and High-Grade Prostate Intraepithelial Neoplasm Patients

Objective: Atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) are two pathological findings occasionally noted in prostate biopsies. Previous Western studies reported that they were associated with prostate cancer. However, none Taiwanese series report the subsequent cancer detection in ASAP and HGPIN patients. This study aimed to examine the results of repeated biopsies in the patients with ASAP and HGPIN. Materials and Methods: A total of 220 consecutive patients with ASAP and/or HGPIN at our institute between January 1990 and December 2010 were enrolled. Patient demographics and clinical information were extracted from the electronic database of our institute. Prostate biopsies were performed through transrectal ultrasound guidance. The patients who had concurrent prostate cancer (n = 51) and no repeated prostate biopsies (n = 103) were excluded from the study. Patients with biopsy pathologies reporting low-grade prostatic intraepithelial neoplasia (n = 2) were also excluded. The remaining 64 patients were available for the final analysis. Results: Nearly, 38, 24, and 2 patients were initially diagnosed as ASAP, HGPIN, and ASAP along with HGPIN, respectively. After 10 years of follow-up, 36.8% patients in ASAP group developed prostate cancer, while 16.7% in HGPIN group and 100% in ASAP + HGPIN group. Median time to developing prostate cancer were 20 months in ASAP group, 31 months in HGPIN group, and 48 months in ASAP + HGPIN group. There was no significant difference of prostate cancer development between ASAP and HGPIN group (P = 0.291). Only older age, classified by 65 years, was significantly associated with a higher detection rate of prostate cancer. Conclusion: Patients with the initial diagnosis of ASAP or PIN has a high risk of developing prostate cancer. Therefore, those patients should be well announced and followed regularly.

Characteristics of serum PSA in HGPIN patients and the effect of the number of the first time biopsy HGPIN positive needles on the detection rate of second biopsy PCa

Objective To investigate characteristics of serum prostate specific antigen (PSA) in HGPIN patients and the effect of the number of the first time biopsy high grade prostatic intraepithelial neoplasia (HGPIN) positive needles on the detection rate of secondary biopsy prostate cancer (PCa). Methods A total of 320 patients who underwent prostate biopsy in our hospital from February 2013 to December 2015 were selected. Ultrasound guided prostate biopsy was performed in all patients, and the differences of serum PSA was analyzed, non PCa patients after 6 months of treatment underwent the secondary biopsy. Results All patients for the first time biopsy results showed: 80 patients with HGPIN ( 51 cases of solitary type and 29 cases of multifocal type ), 45 cases of low grade prostatic intraepithelial neoplasia (LGPIN), 128 cases of benign prostatic hyperplasia (BPH), 67 cases of PCa. Serum PSA of patients with PCa was significantly higher than that of BPH, LGPIN, solitary and multifocal HGPIN patients (P 0.05). PCa proportion of secondary biopsy in multifocal HGPIN patients was 38.46%, significantly higher than BPH, LGPIN and solitary HGPIN patients (P 0.05). Conclusions Serum PSA level of multifocal HGPIN patients is higher than solitary HGPIN, BPH and LGPIN, but still lower than PCa. Detection rates of secondary biopsy PCa in multifocal HGPIN patients are significantly higher than other patients. Key words: Prostatic Neoplasms; Prostate-Specific Antigen; Biopsy, Needle

Chemoprevention of prostate cancer in men with high-grade prostatic intraepithelial neoplasia (HGPIN): a systematic review and adjusted indirect treatment comparison.

BackgroundHigh-grade prostatic intraepithelial neoplasia (HGPIN) is the precursor or premalignant form of prostate cancer. At least 30% patients with a confirmed HGPIN will develop prostate cancer within 1 year after repeated biopsy. HGPIN patients are the appropriate at-risk population for chemoprevention strategies investigation against prostate cancer. However the commonly used chemoprevention agents that targeted on hormonal imbalance or lifestyle-related factors showed varied results in HGPIN patients.MethodsLiterature searches were conducted in PubMed, EMBASE and Cochrane library according to Cochrane guidelines before January 31st, 2017. Direct meta-analysis were performed to summarize the efficacy of candidate chemopreventative agents Dutasteride, Flutamide, Toremifene, Selenium, Green tea components, Lycopene and natural food products combination. Adjusted indirect meta-analyses were employed to compare the relative efficacy of these candidate chemoprevention agents head-to-head.ResultsThe overall incidence of prostate cancer in HGPIN was slightly decreased by chemoprevention agents (25.7% vs 31.5%, RR = 0.92, 95% CI: 0.83-1.03, P = 0.183), with minor heterogeneity (I2 = 22.3%, χ2 = 15.08, P = 0.237), but without statistical significance. Subgroup analysis showed that green tea catechins significantly decreased prostate cancer in HGPIN patients (7.60% vs 23.1%, RR = 0.39, 95% CI: 0.16-10.97, P P = 0.044), with moderate heterogeneity (I2 = 47.9%, χ2 = 1.92, P = 0.166). The adjusted indirect meta-analysis favored green tea catechins over other chemoprevention agents, and significantly when compared to natural food products combination (RR = 0.355, 95% CI: 0.134-0.934).ConclusionThe overall efficacy of chemoprevention agents in HGPIN patients is limited. But Green tea catechins showed the superiority to decrease prostate cancer in HGPIN patients.

Features of serum PSA in HGPIN patients and the influencce of HGPIN positive needle biopsy unmber on the detection rate of PCa

Objectives To study features of serum prostate specific antigen (PSA) characteristics in high grade prostatic intraepithelial neoplasia (HGPIN) and the first needle biopsy HGPIN positive number on prostate cancer (PCa) detection rate. Methods 551 patients with suspected PCa were diagnosed by biopsy. According to the diagnostic results, the detection rate of PCa was compared between the serum PSA level of each group and the HGPIN positive needle array in the first time. Results Biopsy results showed that 37.0% (204/551) of patients were PCa, 43.6% (240/551) of patients were benign prostatic hyperplasia (BPH) and 10.7% (59/551) of patients were low grade prostatic intraepithelial neoplasia (LG PIN). In those 48 cases of HG PIN patients, 28 cases were one positive needle, 13 cases were two positive needles, 7 cases were three or more positive neddles. Patients with PCa, two or more positive needles had significantly higher PSA level(P<0.05). The return visit of PCa detection rate were 12.8%(6/47) in BHP patients. In LG PIN were 10.3% (3/29), unifocal HGPIN patients were 10.7% (3 / 28), bifocal HGPIN patients were 23.1% (3 / 13), trifocal and above HGPIN patients were 57.1% (4 / 7). Conclusions The level of serum PSA in unifocal HG PIN patients is low, and the level of PSA in the multi focal HGPIN is increased, and the detection rate of PCa is increased during the multiple HGPIN biopsy. Key words: Prostatic Neoplasms; Prostate-Specific Antigen; Biopsy, Needle

MP86-02 PREDICTIVE VALUE OF PATHOLOGIC PARAMETERS AND ERG ONCOPROTEIN EXPRESSION IN THE STRATIFICATION OF PROSTATE CANCER RISK ASSOCIATED WITH HIGH GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA (HGPIN) DIAGNOSIS IN PROSTATE NEEDLE BIOPSY

You have accessJournal of UrologyProstate Cancer: Detection and Screening VII1 Apr 2015MP86-02 PREDICTIVE VALUE OF PATHOLOGIC PARAMETERS AND ERG ONCOPROTEIN EXPRESSION IN THE STRATIFICATION OF PROSTATE CANCER RISK ASSOCIATED WITH HIGH GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA (HGPIN) DIAGNOSIS IN PROSTATE NEEDLE BIOPSY Rajal Shah and Savvas Mendrinos Rajal ShahRajal Shah More articles by this author and Savvas MendrinosSavvas Mendrinos More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1911AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES HGPIN diagnosis in prostate needle biopsy (NBX) has traditionally been associated with high predictability of finding a cancer (PCa) in repeat biopsy (∼40%); however, the diagnosis rates of PCa after an initial diagnosis of HGPIN have significantly decreased in recent years (∼25%) as more aggressive biopsy templates have reduced the number of cancers missed on initial biopsy. However, there is still considerable heterogeneity in practices regarding management of HGPIN. Which patients with the HGPIN diagnosis should be biopsied remain a clinical management dilemma. ERG is a highly PCa specific marker that is present in ∼50% of prostate carcinomas (PCas) and ∼20% of high-grade prostatic intraepithelial neoplasia (HGPIN) that intermingle with PCa. METHODS 107 patients with HGPIN in initial biopsy and at least one follow-up biopsy were included. Clinicopathologic features including age, serum PSA, number of cores with HGPIN, laterality of involvement and presence or absence of ERG overexpression by immunostaining (IHC) were analyzed in order to identify parameters that correlate with subsequent detection of PCa. RESULTS The mean age was 63 years (range, 46 - 83). The repeat biopsy was performed at mean of 5.5 months (range, 1 - 26). A mean of 10.5 and 10.8 cores for initial and repeat biopsy were obtained (range, 6 - 24). Twenty five (23%) had cancer, 9 (8.4%) had HGPIN, and 73 (68%) had benign diagnosis on repeat biopsy. ERG expression was present in 9 (8%) HGPIN patients; PCa was found in 7 (77%) subsequent biopsies. Of 98 biopsies with negative ERG staining, PCa was found in 16 (15%) subsequent biopsies. Of 25 patients with subsequent cancer diagnosis, 14 (56%) had >1 site with HGPIN and 11 (44%) had bilateral involvement. Of 82 patients with no cancer on follow-up repeat biopsy, 32 (39%) had >1 site with HGPIN and 12 (15%) had bilateral disease. Only 6 (6%) patients with single site (core) with HGPIN had PCa on repeat biopsy. The combination of > 1 core with HGPIN and/or bilateral involvement with ERG positivity was associated with the presence of PCa in 100% of repeat biopsies. CONCLUSIONS Our preliminary results support utility of the ERG IHC along with pathological parameters to tailor management of patients with HGPIN on the initial biopsy. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e1075 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rajal Shah More articles by this author Savvas Mendrinos More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Abstract 2175: Prospective association between obesity and statin use with conversion from high-grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer (PC)

Abstract BACKGROUND: HGPIN shares many phenotypic and genetic traits with PC, and historically, a patient with HGPIN at biopsy was at high-risk for PC at future biopsy. Although obesity and certain medications have been associated with PC risk, no lifestyle or chemoprevention recommendations are available to prevent PC in high-risk men with HGPIN. OBJECTIVE: Determine the prospective association between obesity and medication use for obesity-related comorbidities with the conversion from HGPIN to PC at follow-up. METHODS: Men seeking a prostate biopsy were targeted for recruitment. After consent, we measured weight, height, sitting height, and waist and hip circumferences, and demographics by questionnaire. Pathology charts were reviewed to identify patients with HGPIN and without PC or other suspicious findings. Medication use for diabetes, BPH, high cholesterol, and hypertension at recruitment were extracted from medical charts. There were 105 HGPIN patients with at least one follow-up prostate biopsy and thus with a potential for PC at follow-up. Multivariable logistic regression was used to determine the association between body size and medication use with PC risk, controlling for age at recruitment, number of follow-up biopsies (1, 2, &amp;gt;2), PSA (ng/ml), and prostate size (mls). RESULTS: Average age, PSA level, and prostate size were 65 years, 6.4 ng/ml, and 49 mls, respectively. Median follow-up was 5 years, and 13 patients had more than one follow-up biopsy. During follow-up, 45 men were diagnosed with PC. Increasing waist-hip ratio (WHR) was significantly associated with conversion from HGPIN to PC (OR = 2.26 (1.14, 4.47), p=0.02, per 0.1 increase in WHR). Men with a WHR &amp;gt; 1.00 were 2.7 times more likely to be diagnosed with PC compared to men with a WHR=&amp;lt;1.00 (p=0.02). Waist circumference (WC) was marginally associated with conversion to PC (OR = 1.04 (1.00, 1.08), p=0.05, per cm). BMI, height, and sitting height were not significantly associated with PC. Furthermore, use of statins or anti-hypertensive medications at baseline were marginally significantly associated with a lower PC risk (Statin: OR=0.43 (0.18, 1.06), p=0.06; HTN: OR=0.47 (0.20, 1.09), p=0.08). In contrast, diabetes and BPH medications, or regular aspirin use, were not associated with PC. Strengths include systematic HGPIN evaluation from one pathologist, little patient migration, measured body size, and medical chart data. However, inference is restricted to those HGPIN patients who received a follow-up biopsy. CONCLUSION: Centralized obesity measured as WHR increased the risk of PC among HGPIN patients, while statins and hypertension medications were associated marginally with lower PC risk. The role of hyperlipidemia and statins in PC progression following HGPIN development requires further investigation. Citation Format: Jay H. Fowke, Saundra Motley, Susan Byerly. Prospective association between obesity and statin use with conversion from high-grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer (PC). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2175. doi:10.1158/1538-7445.AM2014-2175

Subsequent prostate cancer detection in patients with prostatic intraepithelial neoplasia or atypical small acinar proliferation

To evaluate the predictors of prostate cancer in follow-up of patients diagnosed on initial biopsy with high-grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation (ASAP). We studied 201 patients with HGPIN and 22 patients with ASAP on initial prostatic biopsy who had subsequent prostatic biopsies. The mean time of follow-up was 17.3 months (range 1-62). The mean number of biopsy sessions was 2.5 (range 2-6), and the median number of biopsy cores was 10 (range 6-14). On subsequent biopsies, the rate of prostate cancer was 21.9% (44/201) in HGPIN patients. Of these, 32/201 patients (15.9%), 9/66 patients (13.6%) and 3/18 patients (16.6%) were found to have cancer on the first, second and third follow-up biopsy sessions, respectively. In ASAP patients, the cancer detection rate was 13/22 (59.1%), all of whom were found on the first follow-up biopsy. There was a statistically significant difference between the cancer detection rate in ASAP and HGPIN patients (p < 0.001). Multivariate analysis showed that the independent predictors of cancer were the number of cores in the initial biopsy, the number of cores (> 10) in the follow-up biopsy and a prostate specific antigen (PSA) density of >/= 0.15 (odds ratio 0.77, 3.46 and 2.7,8 respectively; p < 0.04). Conversely, in ASAP patients none of these variables were found to be associated with cancer diagnosis. ASAP is a strong predictive factor associated with cancer when compared with HGPIN. The factors predictive of cancer on follow-up biopsy of HGPIN are number of cores on initial biopsy, more than 10 cores in rebiopsy and elevated PSA density. As the cancer detection rate on repeated biopsy of HGPIN patients is the same as that of patients without HGPIN, perhaps the standard of repeat biopsy in all patients with HGPIN should be revisited.

Detection of Alpha-Methylacyl-CoA Racemase (AMACR), a Biomarker of Prostate Cancer, in Patient Blood Samples Using a Nanoparticle Electrochemical Biosensor.

Although still commonly used in clinical practice to screen and diagnose prostate cancer, there are numerous weaknesses of prostate-specific antigen (PSA) testing, including lack of specificity and the inability to distinguish between aggressive and indolent cancers. A promising prostate cancer biomarker, alpha-methylacyl-CoA racemase (AMACR), has been previously demonstrated to distinguish cancer from healthy and benign prostate cells with high sensitivity and specificity. However, no accurate clinically useful assay has been developed. This study reports the development of a single use, disposable biosensor for AMACR detection. Human blood samples were used to verify its validity, reproducibility and reliability. Plasma samples from 9 healthy males, 10 patients with high grade prostatic intraepithelial neoplasia (HGPIN), and 5 prostate cancer patients were measured for AMACR levels. The average AMACR levels in the prostate cancer patients was 10 fold higher (mean(SD) = 0.077 (0.10)) than either the controls (mean(SD) = 0.005 (0.001)) or HGPIN patients (mean(SD) = 0.004 (0.0005)). At a cutoff of between 0.08 and 0.9, we are able to achieve 100% accuracy in separating prostate cancer patients from controls. Our results provide strong evidence demonstrating that this biosensor can perform as a reliable assay for prostate cancer detection and diagnosis.

Predicting prostate biopsy outcome: prostate health index (phi) and prostate cancer antigen 3 (PCA3) are useful biomarkers

Indication for prostate biopsy is presently mainly based on prostate-specific antigen (PSA) serum levels and digital-rectal examination (DRE). In view of the unsatisfactory accuracy of these two diagnostic exams, research has focused on novel markers to improve pre-biopsy prostate cancer detection, such as phi and PCA3.The purpose of this prospective study was to assess the diagnostic accuracy of phi and PCA3 for prostate cancer using biopsy as gold standard.Phi index (Beckman coulter immunoassay), PCA3 score (Progensa PCA3 assay) and other established biomarkers (tPSA, fPSA and %fPSA) were assessed before a 18-core prostate biopsy in a group of 251 subjects at their first biopsy.Values of %p2PSA and phi were significantly higher in patients with PCa compared with PCa-negative group (p<0.001) and also compared with high grade prostatic intraepithelial neoplasia (HGPIN) (p<0.001). PCA3 score values were significantly higher in PCa compared with PCa-negative subjects (p<0.001) and in HGPIN vs PCa-negative patients (p<0.001). ROC curve analysis showed that %p2PSA, phi and PCA3 are predictive of malignancy.In conclusion, %p2PSA, phi and PCA3 may predict a diagnosis of PCa in men undergoing their first prostate biopsy. PCA3 score is more useful in discriminating between HGPIN and non-cancer.

Implication of High Grade Intraepithelial Neoplasia in Adverse Pathology after Radical Prostatectomy

The implication of high grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer aggressiveness and prognosis is conflicted. The aim of the present study was to evaluate the role of HGPIN in prediction of adverse pathology in patients undergoing a radical prostatectomy. We retrospectively analysed patients who underwent a radical prostatectomy between January 2005 and December 2010. The relationship between HGPIN and the presence of upgrade, positive surgical margins (PSM), extracapsular disease (ECD), seminal vesicle invasion (SVI) and lymph node invasion (LNI) was analysed. HGPIN predictive ability was estimated by using receiver operating characteristic curves. HGPIN was found in 160 (53.3%) specimens. A statistically significant correlation was found between HGPIN and preoperative prostate specific antigen (p=0.020) and patients' age (p=0.025). No significant differences were found, regarding the presence of adverse pathological findings, between the patients with or without HGPIN, irrespective of the preoperative risk stratification. HGPIN did not reach significance for the prediction of upgrade, PSM, ECD, SVI and LNI. The presence of concomitant HGPIN and prostate cancer found not to be related with tumor aggressiveness in patients undergoing a radical prostatectomy and should not be considered as a parameter for the operative outcome prediction.

Association of Pb, Cd, and Se Concentrations and Oxidative Damage-Related Markers in Different Grades of Prostate Carcinoma

Prostate cancer is known to be affected by the heavy metal levels and oxidative damage of the body, yet there are very few studies which look into the way it occurs. The aim of this study was to determine whether blood and tissue lead (Pb), cadmium (Cd), and selenium (Se) levels are associated with oxidative damage in the context of prostate cancer progression and development. Seventy-nine patients comprising 25 patients with benign prostatic hypertrophy (BPH), 23 patients with malignant prostatic carcinoma (malign Ca), 16 patients with low-grade prostatic intraepithelial neoplasia (LGPIN), and 15 patients with high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosed on the basis of their clinical profile, transrectal ultrasonography, and histopathology were included in this study. Cd and Pb levels in whole blood were found to be increased in patients with HGPIN compared with the BPH group; also, the levels of Cd in whole blood and tissue were found to be increasing in patients with malign Ca, unlike BPH patients. Moreover, the levels of malondialdehyde (MDA) in plasma and tissue were significantly increased in malign Ca, LGPIN, and HGPIN than those in BPH. However, the levels of tissue Pb were found to be decreasing in BPH, unlike the malign Ca and HGPIN patients, and the levels of tissue protein carbonyls in malign Ca were significantly lower than those in HGPIN. The levels of tissue reduced glutathione (GSH) in malign Ca were significantly lower than those in BPH. Additionally, the levels of Se in serum and tissue in LGPIN were significantly lower than those in BPH. The serum Se levels in HGPIN were also significantly lower than those in BPH and malign Ca groups. Furthermore, the concentrations of serum Se in LGPIN were significantly lower than those in malign Ca. From the Pearson correlation analysis, there were significant positive correlations between tissue Cd and MDA levels in malign Ca, LGPIN, and HGPIN and between the tissue Pb and tissue MDA and protein carbonyl levels in malign Ca. Blood Pb and tissue Pb were also significantly positively correlated with plasma MDA and protein carbonyl levels in malign Ca. In addition, blood Pb was significantly positively correlated with tissue MDA and protein carbonyl levels in malign Ca, and a significant positive correlation was also found between blood Cd and plasma protein carbonyls and tissue MDA in LGPIN. We observed that altered prooxidant-antioxidant balance and heavy metal levels may lead to an increase in oxidative damage and may consequently play an important role in prostate carcinogenesis. These findings indicate that changes in the levels of Pb, Cd, Se, MDA, protein carbonyls, and GSH in the blood and/or tissue are related to the prostatic carcinoma development and progression, although triggering one of the mentioned changes is unknown; therefore, further study is required to determine the exact steps of the process and clarify the roles of different substances in order to obtain a more detailed explanation of the phenomenon.

Increased serum level of early prostate cancer antigen is associated with subsequent cancer risk in men with high-grade prostatic intraepithelial neoplasia

Early prostate cancer antigen (EPCA) has been recently suggested as a novel biomarker in malignant and premalignant lesions of the prostate. This study was to examine serum expression of EPCA and to further clarify the relationship between initial serum EPCA levels and the presence of subsequent cancer in the individuals with isolated high-grade prostatic intraepithelial neoplasia (HGPIN). An indirect ELISA was used for initial serum EPCA measurement in 112 men with isolated HGPIN, who were enrolled and completed a follow-up of >or=5 years. All patients had a detectable concentration of EPCA in the initial serum, with a mean of 0.64+/-0.13 absorbance at 450 nm. Thirty-three patients had an initial serum EPCA level of >or=1.10, in which 31 cases were subsequently identified as having prostate cancer on follow-up. However, in the remaining 79 cases, serum EPCA levels were all <1.10, and none was diagnosed with cancer later. Statistical analysis showed a significantly higher serum ECPA level in isolated HGPIN patients with subsequent cancer than those without cancer (P<0.001). The area under the receiver operating characteristic curves showed that serum EPCA level had better predictive accuracy of cancer onset on follow-up than prostate specific antigen velocity and abnormal digital rectal examination findings. Furthermore, univariate and multivariate Cox regression analyses demonstrated the predictive performance independently by initial serum EPCA>or=1.10 absorbance (relative risk, 3.32; 95% confidence intervals, 2.62-5.03, P<0.001). These preliminary findings first show the potential of serum EPCA to serve as a significant predictor for subsequent cancer in isolated HGPIN.

Unfavorable Prognostic Value of Human PEDF Decreased in High-Grade Prostatic Intraepithelial Neoplasia: A Differential Proteomics Approach

Background: High-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precursor of prostate cancer, but the frequency and timing of epigenetic changes found in prostate carcinogenesis has not been extensively documented. Methods: Here, we performed a differential proteomic profiling study on the serum of HGPIN and prostate cancer patients. Eleven HGPIN patients were enrolled, their serum protein patterns (2D-electrophoresis and mass spectroscopy) were compared with fifteen prostate cancer patients, and the follow-up study was further performed in the HGPIN patients. Results: We described eleven altered protein spots in these two groups, in which pigment epithelium-derived factor (PEDF) was found to be significantly down-regulated in prostate cancer patients, which was further confirmed by ELISA method. In addition, 18.2% (2/11) of the HGPIN revealed strong expression for PEDF, 27.3%(3/11) showed a moderate expression and 54.5% (6/11) a weak PEDF expression in immunohistochemistry study, while in prostatic cancerous cells, 100% patients (15/15) revealed a weak expression for PEDF. The ten months’ follow-up study demonstrated that 2 of 6 HGPIN patients with weakly expressed PEDF were found to have subsequent prostate cancer. Conclusions: our data identified PEDF in HGPIN as a significant predictor of subsequent cancer, suggesting that PEDF implies in prostatic tumorigenesis and may be used to identify the patients with isolated HGPIN who are at high risk for cancer onset in the disease process.