Comparison of the Formula of PSA, Age, Prostate Volume and Race Versus PSA Density and the Detection of Primary Malignant Circulating Prostate Cells in Predicting a Positive Initial Prostate Biopsy in Chilean Men with Suspicion of Prostate Cancer

Murray, Nigel P,Reyes, Eduardo,Fuentealba, Cynthia,Orellana, Nelson,Morales, Francisca,Jacob, Omar Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.13

Background: Combining risk factors for prostate cancer into a predictive tool may improve the detection of prostate cancer while decreasing the number of benign biopsies. We compare one such tool, age multiplied by prostate volume divided by total serum PSA (PSA-AV) with PSA density and detection of primary malignant circulating prostate cells (CPCs) in a Chilean prostate cancer screening program. The objectives were not only to determine the predictive values of each, but to determine the number of clinically significant cancers that would have been detected or missed. Materials and Methods: A prospective study was conducted of all men undergoing 12 core ultrasound guided prostate biopsy for suspicion of cancer attending the Hospital DIPRECA and Hospital de Carabineros de Chile. Total serum PSA was registered, prostate volumecalculated at the moment of biopsy, and an 8ml blood simple taken immediately before the biopsy procedure. Mononuclear cells were obtained from the blood simple using differential gel centrifugation and CPCs identified using immunocytchemistry with anti-PSA and anti-P504S. Biopsy results were classed as positive or negative for cancer and if positive the Gleason score, number of positive cores and percent infiltration recorded. Results: A total of 664 men participated, of whom 234 (35.2%) had cancer detected. They were older, had higher mean PSA, PSA density and lower PSA-AV. Detection of CPCs had high predictive score, sensitivity, sensibility and positive and negative predictive values, PSA-AV was not significantly different from PSA density in this population. The use of CPC detection avoided more biopsies and missed fewer significant cancers.Conclusions: In this screening population the use of CPC detection predicted the presence of clinically significant prostate cancer better than the other parameters. The high negative predictive value would allow men CPC negative to avoid biopsy but remain in follow up. The formula PSA-AV did not add to the predictive performance using PSA density.

Head to Head Comparison of the Chun Nomogram, Percentage Free PSA and Primary Circulating Prostate Cells to Predict the Presence of Prostate Cancer at Repeat Biopsy

Murray, Nigel P,Reyes, Eduardo,Orellana, Nelson,Fuentealba, Cynthia,Jacob, Omar Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.6

Background: The limitations of total serum PSA values remain problematic, especially after an initial negative prostate biopsy. In this prospective study of Chilean men with a continued suspicion of prostate cancer due to a persistently elevated total serum PSA, abnormal digital rectal examination and initial negative prostate biopsy were compared with the use of the on-line Chun nomagram, detection of primary malignant circulating prostate cells (CPCs) and free percent PSA to predict a positive second prostate biopsy. We hypothesized that men negative for circulating prostate cells have a small risk of clinically significant prostate cancer and thus may be conservatively observed. Men positive for circulating prostate cells should undergo biopsy to confirm prostate cancer. Materials and Methods: Consecutive men with a continued suspicion of prostate cancer underwent 12 core TRUS prostate biopsy; age, total serum PSA and percentage free PSA and Chun nomagram scores were registered. Immediately before biopsy an 8ml blood simple was taken to detect primary mCPCs. Mononuclear cells were obtained by differential gel centrifugation and identified using double immunostaining with anti-PSA and anti-P504S. Biopsies were classifed as cancer/no-cancer, mCPC detecton test as negative/positive and the total number of cells/8ml registered. Areas under the curve (AUC) for percentage free PSA, Chun score and CPCs were calculated and compared. Diagnostic yields were calculated with reference to the number of possible biopsies that could be avoided and the number of clinically significant cancers that would be missed. Results: A total of 164 men underwent a second biopsy; 41 (25%) had cancer; the AUCs were 0.65 for free PSA, 0.76 for the Chun score and 0.87 for CPC detection, the last having a significantly superior prediction value (p=0.01). Using cut off values of free PSA <10%, Chun score >50% and ${\geq}1$ CPC detected, CPC detection had a higher diagnostic yield. Some 4/41 cancers complied with the criteria for active surveillance, free PSA and the Chun score missed a higher number of significant cancers when compared with CPC detection. Conclusions: Primary CPC detection outperformed the use of free PSA and the Chun nomagram in predicting clinically significant prostate cancer at repeat prostate biopsy.

60세 미만 한국인의 전립선암 선별에 있어 전립선특이항원속도의 유용성 및 새로운 절단치

이혜원,곽경원,최윤호,최한용,이현무 대한비뇨의학회 2008 Investigative and Clinical Urology Vol.49 No.2

Purpose: We identified new thresholds for prostate-specific antigen velocity(PSAV) for screening of prostate cancer in Korean patients younger than 60 years old based on PSA serial data obtained from our hospital's health promotion center. Materials and Methods: The study population was retrieved from 10,011 patients, 40 to 79 years old, with 2 or more PSA values within five years who visited our hospital's health promotion center between January 2002 and December 2006, including 100 patients with prostate cancer. These subjects were divided into 2 age groups, 40-59 years old and 60-79 years old, and their PSAV were calculated as the rate of PSA change using the first and last values only. A receiver operating characteristic(ROC) curve was used to analyze the performance of PSAV in the screening of prostate cancer, and we developed new PSAV thresholds by comparing sensitivity and specificity at different PSAV levels. Results: Overall prostate cancer prevalence was 0.6%(45) in younger(40-59 years old) patients and 2.1%(55) in older(60 to 79 years old) patients. The median PSAV in the normal control group and the cancer group were 0.047ng/ml/year vs 0.877ng/ml/year in younger patients(p<0.0001) and 0.067ng/ml/year vs 0.642ng/ml/year in older patients(p<0.0001). For younger patients, the sensitivity and specificity were 55.6% and 99.2% at PSAV 0.75ng/ml/year, but decreasing the PSAV cut-points to 0.35ng/ ml/year improved sensitivity to 78% for cancer detection in this age group. Conclusions: The previous PSAV threshold for prostate biopsy, 0.75 ng/ml/year or greater, probably underestimate cancer risk in younger Korean men. Decreasing PSAV thresholds to 0.35ng/ml/year would improve screening sensitivity. (Korean J Urol 2008;49:113-117) Purpose: We identified new thresholds for prostate-specific antigen velocity(PSAV) for screening of prostate cancer in Korean patients younger than 60 years old based on PSA serial data obtained from our hospital's health promotion center. Materials and Methods: The study population was retrieved from 10,011 patients, 40 to 79 years old, with 2 or more PSA values within five years who visited our hospital's health promotion center between January 2002 and December 2006, including 100 patients with prostate cancer. These subjects were divided into 2 age groups, 40-59 years old and 60-79 years old, and their PSAV were calculated as the rate of PSA change using the first and last values only. A receiver operating characteristic(ROC) curve was used to analyze the performance of PSAV in the screening of prostate cancer, and we developed new PSAV thresholds by comparing sensitivity and specificity at different PSAV levels. Results: Overall prostate cancer prevalence was 0.6%(45) in younger(40-59 years old) patients and 2.1%(55) in older(60 to 79 years old) patients. The median PSAV in the normal control group and the cancer group were 0.047ng/ml/year vs 0.877ng/ml/year in younger patients(p<0.0001) and 0.067ng/ml/year vs 0.642ng/ml/year in older patients(p<0.0001). For younger patients, the sensitivity and specificity were 55.6% and 99.2% at PSAV 0.75ng/ml/year, but decreasing the PSAV cut-points to 0.35ng/ ml/year improved sensitivity to 78% for cancer detection in this age group. Conclusions: The previous PSAV threshold for prostate biopsy, 0.75 ng/ml/year or greater, probably underestimate cancer risk in younger Korean men. Decreasing PSAV thresholds to 0.35ng/ml/year would improve screening sensitivity. (Korean J Urol 2008;49:113-117)

전립선 암종의 신생혈관 형성과 세포 증식능 및 전립선특이항원 발현정도가 종양전이 및 예후에 미치는 영향

유탁근,이춘용,장세진,박문향 한양대학교 의과대학 1999 한양의대 학술지 Vol.19 No.1

Prostate adenocarcinoma is a significant cause of morbidity and mortality in old men. Recently, with increased screening, there has been much interest in early detection and proper management of this cancer. The best predictors of prognosis in prostate cancer are the stage of disease and histologic differentiation of the cancer. But, preoperative prediction of pathologic stage in prostate cancer is currently limited and histologic differentiation may be somewhat subjective. Therefore, more accurate predictors of biological progression are needed. A number of markers including DNA ploidy, prostate specific antigen(PSA) level, oncogenes, tumor suppressor genes and expression of proteins related to proliferation have been suggested to aid the stage and histologic differentiation in predicting the malignant potential of prostate cancers. The authors designed this study to determine the prediction efficacies of neovascularity, proliferating cell nuclear antigen(PCNA) labeling index and intensity of PSA reaction using immunohistochemical staining, To evaluated above mentioned 3 markers, immunohistochemical stains in 48 cases of prostate cancers and 5 cases of benign prostatic hyperplasia(BPH) were performed and analysed. Microvessels were identified by immunostaining of endothelial cells for factor Ⅷ-related antigen. PCNA labeling indices were obtained in 200X field by counting more than 1,000 cells. The intensity of PSA staining was graded as 0, 1, 2, 3, based on its relationship to the control, and used as scores. The most outstanding staining was considered as 3. The results were as follows: 1. The mean microvessel count(MVC) in BPH group was 34.2±5.9 per 200X field and that of prostate cancer group was 63.5±38.6(p〈0.05). The mean MVC of Gleason grade I prostate cancer was 32.2(16-40). The MVCs were 38.3(23-58), 58.8(23-92), 78.1(18-182) and 86.8(22-180), from grade Ⅱ to V respectively. According to stage, the mean MVCs were 40.8, 48.5, 55.0 and 89.0 from A to D. Between the 2 groups with well differentiated(grade I-Ⅲ) and poorly differentiated(grade Ⅳ-Ⅴ) prostate cancer, there was significant difference in MVC(p〈0.05). And between localized and metastatic group, there was also significant difference. The mean survival of high MVC(MVC≥60) group was 57.4±15.9 months and that of low MVC group was 74.0±11.2 months. But the difference was not statistically significant. 2. The mean PCNA labeling indices were 14.6±8.0% in BPH group and 32.3±15.4% in prostate cancer group. According to Gleason grade, the mean PCNA labeling indices showed the distribution of 33.4(11-55)%, 30.8(19-41)%, 26.3(8-74)%, 38.0(22-55)% and 36.6(12-72)% from I to V respectively. According to stage, the mean value of stage A was 23.1(11-55)%. The mean values were 27.4(8-41)%, 30.4(21-51%) and 36.2(8-74)% in stage B, C and D. Between localized and metastatic group, the difference of PCNA labeling index was not statistically significant. The mean survival of high labeling index(≥30%) group was 66.0±12.2 months contrasted with 72.4±14.6 months of low labeling index group(p〉0.05). 3. The intensities of PSA staining were as follows: according to grade, from I to V, they were 2, 20, 2.75, 2.50, 1.73 and 1.20, respectively. In stage A, the mean PSA score was 2.67, and those of other stages were 2.62 in B, 2.60 in C and 1.58 in D. Between the 2 groups with well differentiated and poorly differentiated prostate cancer, there was significant differnce in PSA score(p〈0.05). And between localized and metastatic group, there was also significant difference. The mean survival of high intensity(2, 3) group was 74.1±11.6 months contrasted with 48.9±11.5 months in low intensity group(0, 1). But the difference was not statistically significant. These results suggest that microvessel density in prostate adenocarcinoma may be an another prognostic factor supporting clinical stage and histologic differentiation. In addition, the intensity of PSA immunostaining can be used as a predictor of malignant potential. But relatively negative results were obtained for PCNA labeling index from this study. To further define MVC and PSA staining intensity as predictors of prostate cancer, more enthusiastic and well designed studies are needed.

전립선암의 진단에서 경직장초음파검사 소견 상 저반향 부위의 의의

이활,이경섭 大韓泌尿器科學會 2000 Korean Journal of Urology Vol.41 No.4

전립선특이항원치 4.0ng/ml 이상인 환자에서 전립선용적과 나이에 따른 전립선암의 발견율

윤병일,김수진,조혁진,홍성후,손동완,이지열,황태곤,김세웅 대한남성과학회 2010 The World Journal of Men's Health Vol.28 No.1

Purpose: We retrospectively investigated the changes of prostate cancer detection rate according to patients prostate volume, age with prostate-specific antigen (PSA) levels of above 4.0ng/ml. Material and Methods: Data were collected from 663 patients who underwent 10 core prostate biopsy for elevated PSA above 4.0ng/ml. The biopsy-proven cancer patient group was compared to the non-cancer patient group according to age, PSA, prostate volume and PSAD. Prostate cancer detection rate was calculated according to prostate volume (less than 40 vs 40 or more 40ml) and age (less than 60, 60-69, 70-79, 80 or more years old). Also we compared prostate cancer detection rate according to PSA levels (4-10 vs 10-20ng/ml). Results: Among the 663 patients who underwent prostate biopsy, prostate cancer was detected in 134 patients (20.2%). There were no stastically difference in mean age, mean prostate volume, and mean PSAD except mean PSA (13.9 vs 11.9ng/ml) between cancer and non-cancer groups. The cancer detection rate in small prostate was significantly higher than large prostate (23.5% vs 16.0%). The cancer detection rate was significantly increased with age: from 14.5% for below 60 year-old patients to 30.3% for the 80 or more year-old patients. There was no significant difference in cancer detection rate between the two PSA groups (19.0 vs 20.5%). Conclusion: Prostate cancer detection rate was higher in old patients and patients with small prostate volume. The older age group and the patients with small prostate volume was considered as the important factors to decide whether biopsy of prostate is needed.

Enhancing Knowledge, Beliefs, and Intention to Screen for Prostate Cancer via Different Health Educational Interventions: a Literature Review

Saleh, Ahmad M,Fooladi, Marjaneh M,Petro-Nustas, Wasileh,Dweik, Ghadeer,Abuadas, Mohammad H Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.16

Background: Prostate cancer is one of the most common cancers affecting men globally, constituting the sixth leading cause of cancer related death in males, and the eleventh leading cause of death from cancer in all age groups. In Jordan, prostate cancer is the third most common cancer in the male population, accounting for one third (6.2%) of cancer related deaths and in 2010 alone, 218 (9.4%) new cases were identified. Objective: To assess the effectiveness of different health education interventions aimed at enhancing knowledge, beliefs and intention to screen for prostate cancer. Materials and Methods: A literature search from January 2000 to April 2015 was conducted using the key words "prostate disease," "educational program," "knowledge," "prostate cancer," "demographic factors and prostate cancer," "knowledge and prostate cancer," "education for patients with prostate cancer," "factors that affect intention to screen," "knowledge, beliefs, and intention to screen for prostate cancer," "impact of prostate educational program on beliefs," and "impact of educational program on intention to screen." Results: Majority of studies reviewed indicated that men had low levels of knowledge regarding prostate cancer, and mild to moderate beliefs with good intention to screen for prostate cancer. Conclusions: Most studies indicated that men's knowledge levels about prostate cancer were poor and they had mild to moderate beliefs and intentions to screen for prostate cancer. Therefore, development of an assessment strategy based on the Health Belief Model seems essential. An effectively designed and implemented educational program can help identify the needs and priorities of the target population.

Identification of Prostate Cancer LncRNAs by RNA-Seq

Hu, Cheng-Cheng,Gan, Ping,Zhang, Rui-Ying,Xue, Jin-Xia,Ran, Long-Ke Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21

Purpose: To identify prostate cancer lncRNAs using a pipeline proposed in this study, which is applicable for the identification of lncRNAs that are differentially expressed in prostate cancer tissues but have a negligible potential to encode proteins. Materials and Methods: We used two publicly available RNA-Seq datasets from normal prostate tissue and prostate cancer. Putative lncRNAs were predicted using the biological technology, then specific lncRNAs of prostate cancer were found by differential expression analysis and co-expression network was constructed by the weighted gene co-expression network analysis. Results: A total of 1,080 lncRNA transcripts were obtained in the RNA-Seq datasets. Three genes (PCA3, C20orf166-AS1 and RP11-267A15.1) showed a significant differential expression in the prostate cancer tissues, and were thus identified as prostate cancer specific lncRNAs. Brown and black modules had significant negative and positive correlations with prostate cancer, respectively. Conclusions: The pipeline proposed in this study is useful for the prediction of prostate cancer specific lncRNAs. Three genes (PCA3, C20orf166-AS1, and RP11-267A15.1) were identified to have a significant differential expression in prostate cancer tissues. However, there have been no published studies to demonstrate the specificity of RP11-267A15.1 in prostate cancer tissues. Thus, the results of this study can provide a new theoretic insight into the identification of prostate cancer specific genes.

Expressional and mutational analyses of <i>ATG5</i> gene in prostate cancers

KIM, MIN SUNG,SONG, SANG YONG,LEE, JI YOUL,YOO, NAM JIN,LEE, SUG HYUNG Blackwell Publishing Ltd 2011 APMIS Vol.119 No.11

<P>Kim MS, Song SY, Lee JY, Yoo NJ, Lee SH. Expressional and mutational analyses of <I>ATG5</I> gene in prostate cancers. APMIS 2011; 119: 802–7.</P><P>Autophagy is an evolutionarily conserved mechanism that plays important roles in both cell death and cell survival. ATG5 is an essential constituent for autophagosome formation, which sequesters cytoplasmic materials before lysosomal delivery. Although both cell death and survival are important in cancer development, the role of autophagy in prostate cancer development remains unclear. The aim of this study was to see whether alterations of ATG5 protein expression and somatic mutations of the <I>ATG5</I> gene are found in prostate cancers. In the present study, we analyzed ATG5 protein expression in 107 prostate carcinomas by immunohistochemistry; additionally, we assayed the presence of <I>ATG5</I> somatic mutations in 45 prostate carcinomas by single‐strand conformation polymorphism. Immunostaining of ATG5 in normal prostate cells was observed in 44.9% of the cases, whereas in prostate intraepithelial neoplasm (PIN) and prostate cancer cells, ATG5 was observed in 100% and 89.7% of the cases, respectively. Cytoplasmic expression of ATG5 that might be related to autophagy was seen in PIN (100%) and cancers (83.2%), but not in normal cells (0%). ATG5 expression was not associated with any of the pathologic characteristics, including size of the cancers, age, Gleason score, and stage. As for the <I>ATG5</I> gene, we found no somatic mutations in the prostate cancers. In this study, we analyzed ATG5 expression and mutation in prostate cancers, and found that ATG5 expression was altered in prostate cancers. The expression of ATG5, especially in the cytoplasm, in the prostate cancers compared with normal prostate cells suggested that overexpression of this protein may be related to autophagy and might play a role in prostate tumorigenesis.</P>

전립선암세포에서의 GnRH 및 GnRH 수용체 mRNA 발현의 동정과 전립선암세포의 성장에 미치는 GnRH의 효과

박종윤,현재석,장용우,이현,최봉석,이경익,박형철,백상훈,홍진욱 大韓泌尿器科學會 1997 Korean Journal of Urology Vol.38 No.9