The impact of African American race on prostate cancer detection on repeat prostate biopsy in a veteran population.

PURPOSE: Racial differences in the incidence of prostate cancer on initial biopsy are well established, but the predictive value of African American race on the probability of prostate cancer detection on repeat biopsy is unknown. MATERIALS AND METHODS: At a single institution between January 2007 and June 2014, we reviewed 277 men who first underwent a negative transrectal ultrasound guided needle biopsy of the prostate, and who then subsequently underwent a second biopsy. Detection rates were compared via Chi-square analysis. Race, age, PSA, presence of high-grade prostatic intraepithelial neoplasia, presence of atypical small acinar proliferation, prostate volume, PSA velocity and PSA density were compared via a multivariate logistic regression analysis. RESULTS: 496 AA men and 352 Caucasian men underwent initial biopsy, and AA men had a 49 % cancer detection rate, compared to 34 % in Caucasians (p < 0.0001). AA men also had a greater incidence of Gleason 7 cancers (p = 0.00018) and a smaller mean TRUS volume (p = 0.006) compared to Caucasians. On repeat biopsy, AA men no longer had a higher cancer detection rate (p = 0.227), nor difference in Gleason 7 detection or TRUS volume (p = 0.0992). On initial biopsy, AA race and increasing PSA were both associated with an increased likelihood for cancer detection (p < 0.001 for both). After an initial negative biopsy, AA race no longer predicted for future malignancy detection (p = 0.57), nor did PSA (p = 0.36). CONCLUSIONS: In a cohort of men with high pre-test probability of prostate cancer and an initial negative biopsy, African American race in a veteran population fails to predict the detection of future prostate cancer.

Limited significance of activated Akt-mammalian target of rapamycin signaling pathway in prostate cancer progression.

OBJECTIVE: The objective of this study was to investigate the significance of the activated Akt-mammalian target of rapamycin (Akt-mTOR) signaling pathway in the progression of prostate cancer. MATERIALS AND METHODS: The expression levels of Akt, phosphorylated Akt (p-Akt), mTOR and phosphorylated mTOR (p-mTOR) in 175 prostate specimens, including 61 normal prostate tissues as a control, 24 high-grade prostatic intraepithelial neoplasias (HGPINs) and 90 clinically localized prostate cancers, were evaluated by immunohistochemical staining. p-Akt and p-mTOR ratios, which were defined as the expression level of p-Akt in relation to that of Akt and the expression level of p-mTOR in relation to that of mTOR, respectively, in these specimens were calculated. RESULTS: Expression levels of all four molecules, including Akt, p-Akt, mTOR and p-mTOR, were significantly greater in the HGPIN group compared with the normal control and prostate cancer groups. Furthermore, the p-Akt ratio in the prostate cancer group was significantly lower than that in the HGPIN group, while there was no significant difference in the p-mTOR ratio between the HGPIN and prostate cancer groups. In the prostate cancer group, no significant relationships were observed between major clinicopathological parameters and the expression levels as well as the ratios of p-Akt or p-mTOR. CONCLUSIONS: The Akt-mTOR signaling pathway may play a limited role in the progression of prostate cancer.

Alpha methylacyl-CoA racemase (AMACR) in prostate adenocarcinomas from Japanese patients: is AMACR a "race"-dependent marker?

BACKGROUND: Alpha methylacyl-CoA racemase (AMACR) is a useful diagnostic marker for prostate adenocarcinoma. However, its usefulness has not been fully validated in Japanese patients. The aim of this study was to evaluate the diagnostic utility of AMACR in prostate needle biopsy examination in Japanese patients. METHODS: A total of 119 prospective consecutive prostate needle biopsy specimens (680 cores) obtained from Japanese patients were examined. Sixty patients had adenocarcinoma (adenocarcinoma, 160 cores; benign, 204 cores), 14 patients had high-grade prostatic intraepithelial neoplasia (HGPIN; 19 cores), and 45 patients did not have any neoplastic lesions (297 cores). AMACR expression was scored semi-quantitatively as 0 (no expression), 1+ (partial and/or weak expression), or 2+ (strong, circumferential expression). The number of positively stained glands was counted. RESULTS: 2+ AMACR expression was observed in 70.1% of adenocarcinoma cases and in 52.6% of HGPIN cases. Of the adenocarcinoma cases showing 2+ AMACR expression, 34.8% demonstrated a heterogeneous expression pattern, with 1-75% of AMACR-positive glands. Three hundred eighty-five of the benign glands with an adenocarcinoma component showed 2+ AMACR expression (35 cases, 94 cores). 2+ AMACR expression was observed in 67 non-neoplastic benign glands (9 cases, 19 cores). CONCLUSIONS: The sensitivity and specificity of AMACR for the diagnosis of prostate adenocarcinoma and benign glands in Japanese patients are lower than those previously reported in Western countries. Pathologists should be cautious while interpreting AMACR expression pattern in Japanese patients.

[Constitutional risk factors in prostate cancer]. / Factores de riesgo constitucionales en el cáncer de próstata.

INTRODUCTION: The aim of this review is to update and divulge the main constitutional risk factors involved in the etiopathology of prostate cancer. MATERIALS AND METHODS: Bibliographic review of the scientific literature on the constitutional risk factors associated with prostate cancer between 1985 and 2010, obtained from MedLine, CancerLit, Science Citation Index and Embase. The search profiles were Risk Factors, Genetic Factors, Genetic Polymorphisms, Genomics, Etiology, Epidemiology, Hormonal Factors, Endocrinology, Primary Prevention and Prostate Cancer. RESULTS: The principal constitutional risk factors are: age (before the age of 50 years at least 0.7% of these neoplasms are diagnosed and between 75-85% are diagnosed after the age of 65 years), ethnic-racial and geographic (African Americans present the highest incidence rates, and the lowest are found in South East Asia), genetic, family and hereditary (family syndromes cover 13-26% of all prostate cancers, of which 5% are of autosomal dominant inheritance), hormonal (it is a hormone-dependent tumour), anthropometric (obesity increases the risk), perinatal, arterial hypertension and type 2 diabetes. CONCLUSIONS: Constitutional risk factors play a very important role in the etiopathology of prostate cancer, especially age, ethnic-racial-geographic factors and genetic-family factors. We cannot know what percentage of these neoplasms are a result of constitutional factors, because our knowledge of these factors is currently lacking.

Is high-grade prostatic intraepithelial neoplasia on needle biopsy different in an Asian population: a clinicopathologic study performed in Singapore.

OBJECTIVES: To evaluate the incidence, pathologic findings, and follow-up of high-grade prostatic intraepithelial neoplasia (HGPIN) in a series of prostate core biopsies from Singaporean men. METHODS: We studied isolated HGPIN diagnosed on prostate core biopsies and the incidence of cancer discovered in men who had undergone repeat biopsies from 1999 to 2003 at the Department of Pathology, Singapore General Hospital. RESULTS: Of 1219 men undergoing prostate needle biopsy, 56 (4.6%) had isolated HGPIN. Most cases affected a single prostate core (44 cases, 78.6%). Twenty-nine men (51.8%) underwent repeat biopsies. Cancer was discovered in 7 (24.1%) of the 29 men within two repeat biopsies. CONCLUSIONS: The incidence of isolated HGPIN on prostate needle core biopsies in Asian men, as well as the likelihood of subsequent cancer detection, are comparable to the rates reported for Western populations. The relatively low yield of cancer detection on repeat biopsy supports the need to re-evaluate recommendations for rebiopsy strategies.

Prevalence of prostate cancer and prostatic intraepithelial neoplasia in Caucasian Mediterranean males: an autopsy study.

BACKGROUND: The prevalence of carcinoma of the prostate gland (CaP) and high-grade prostatic intraepithelial neoplasia (HGPIN) was assessed in a Spanish population, representative of the Caucasian Mediterranean (CM) ethnic group. Data were compared with those described in populations from other geographical regions and in other ethnic groups. METHODS: CaP and HGPIN were evaluated in a consecutive series of prostatic glands collected at the post-mortem examination of 162 male patients born and living in Spain, aged 20-80 years, and dying from trauma. The glands were sliced every 2-3 mm. All slices were paraffin embedded and sectioned to obtain 5 microm whole-mount sections. To compare the prevalence rate in our series and in other Caucasian populations with that from other geographical areas and other ethnic groups, we used data from the autopsy study performed at the Wayne State University. RESULTS: Prevalence of CaP is 3.58, 8.82, 14.28, 23.80, 31.7, and 33.33% in the 3rd, 4th, 5th, 6th, 7th, and 8th decades, respectively. The rates of HGPIN were 7.14, 11.75, 35.71, 38.06, 45.40, and 48.15% at the 3rd, 4th, 5th, and 8th decades of life. Both CaP and HGPIN are located preferentially at the peripheral zone of the gland and in 21/27 cases (77.7%), an association between CaP and HGPIN was found. The prevalence of both lesions in CM males is significantly lower than in Caucasian American (CA) and Afro-American (AA) males in all the age groups evaluated. CONCLUSIONS: Microscopic foci of CaP and HGPIN can be documented in CM males from the 3rd decade of life onwards. The lesions become more frequent and extensive as age increases. The prevalence of both lesions seems to be significantly lower in the CM population than in CA and AA males in all the age groups evaluated.

Histological markers of risk and the role of high-grade prostatic intraepithelial neoplasia.

The marked discrepancy between the prevalence of preclinical prostate cancer and the incidence of clinically manifest disease indicates a long latency phase and significant heterogeneity in the progression potential of early neoplastic lesions. There are a variety of histologic changes within prostatic epithelium that have been termed atypical or dysplastic. The 2 most widely studied of these lesions are prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia (AAH). Although associations between AAH and adenocarcinoma are spurious, those linking high-grade PIN (HGPIN) to cancer are far more established. There is a significantly increased risk for patients with isolated HGPIN to have prostate cancer confirmed on subsequent biopsy, suggesting that HGPIN is a marker for prostate carcinoma in addition to its potential role as a premalignant lesion. Autopsy studies reveal that HGPIN is found in association with cancer in 63% to 94% of malignant and 25% to 43% of benign prostates. Data on age and race reveal that African American men develop more extensive HGPIN at a younger age than white men. A wide spectrum of molecular/genetic abnormalities appears to be common to both HGPIN and prostate cancer. Data loss of 8p, 10q, 16q, 18q, and gain of 7q31, 8q, multiple copies of the c-myc genes, along with changes in chromatin texture, telomerase activity, cell cycle status, and proliferative indices collectively suggest that HGPIN is intermediate between benign epithelium and prostatic carcinoma with respect to these markers. These data indicate that HGPIN is important in neoplastic progression, and may present an appropriate target/marker for chemoprevention.

Prospective study of correlations between biopsy-detected high grade prostatic intraepithelial neoplasia, serum prostate specific antigen concentration, and race.

BACKGROUND: High grade prostatic intraepithelial neoplasia (HGPIN), a premalignant lesion of the prostate gland, is more common in black men than in white men. The influence of HGPIN on the serum prostate specific antigen (PSA) concentration is controversial, and correlations between HGPIN and PSA in black men and white men have not been investigated. METHODS: Between January 1992 and December 1998, 411 black men and 639 white men with suspected prostate carcinoma underwent an initial benign prostate biopsy at a single medical center. The presence or absence of HGPIN in the biopsy specimens was determined by one uropathologist. RESULTS: HGPIN was identified in 8.9% of the specimens. When stratified by PSA concentration (< 4.0 ng/mL, 4.0-9.9 ng/mL, and > or = 10.0 ng/mL), HGPIN was associated with an increased PSA concentration only among men with PSA concentrations < 4.0 ng/mL (P = 0.01). The prevalence of HGPIN in the black and white patients was 13.4% and 5.9%, respectively (P < 0.0001), and was significantly greater in black men than in white men with PSA concentrations < 4.0 ng/mL (P = 0.002). Among the patients with PSA concentrations < 4.0 ng/mL, black race was an independent predictor of an increased PSA concentration when adjusted for patient age, prostate volume, and the presence or absence of HGPIN (P = 0.03). CONCLUSIONS: HGPIN is more common in black men than in white men and may produce an increase in the PSA concentration. However, racial differences in the prevalence of HGPIN may not contribute to racial differences in PSA concentrations among men with no clinical or histologic evidence of carcinoma.

Prostatic intraepithelial neoplasia: A marker for high-risk groups and a potential target for chemoprevention.

Both the incidence of, and the mortality due to, prostate cancer in the USA are higher in African-American men than in Caucasian men. This is particularly true in men less than 60 years of age. Our findings indicate that both the prevalence and the extensiveness of high-grade prostatic intraepithelial neoplasia (PIN) are higher in African-American men compared to Caucasians and that this discrepancy starts as early as the third decade of life. In an autopsy series comprising 650 men, extensive high-grade PIN with diffuse involvement of the prostate gland was evident in 25 (7%) of 364 African-American men less than 50 years of age compared to 4 (2%) of 208 Caucasian men in the same age group (p = 0.002). In a series of more than 1,200 men undergoing radical prostatectomy for clinically localized prostate cancer, extensive high-grade PIN was significantly and consistently higher in the African-American cohort than the Caucasian cohort. The difference was more evident in younger patients and those with smaller, organ-confined tumors. In a subset of 216 men (71 African-Americans and 138 Caucasians) with clinical stage T1C prostate cancer, extensive high-grade PIN was identified in 33% and 12% of the two groups respectively (p = 0.001). Moreover, in patients with organ-confined disease, both Gleason score and the extensiveness of high-grade PIN were significant predictors of biochemical recurrence. Our findings suggest an important role for high-grade PIN in the development of clinically significant, potentially aggressive prostate cancer in African-American men. In this epidemiologically identifiable high-risk group, there is a potential opportunity for chemoprevention strategies in younger men with high-grade PIN.

Epidemiology of high grade prostatic intraepithelial neoplasia.

The prevalence of high grade prostatic intraepithelial neoplasia (HGPIN), the age at which this lesion starts and the potential racial or ethnic differences in its distribution are poorly documented. HGPIN is becoming increasingly implicated as a premalignant lesion for clinically significant prostatic carcinoma (PCa) with mounting evidence linking it to carcinoma according to morphologic immunohistochemical and recent genomic studies. We describe our experience with the age and race distribution of HGPIN resulting from two study populations of African-American (AA) and Caucasian (C) males. The first component of this report describes an autopsy study aimed at determining the prevalence of latent PCa and HGPIN in AA and C men 20 years of age or older; 370 (218 AA and 152 C) consecutive step-sectioned, totally embedded prostate glands were microscopically evaluated and mapped for HGPIN and PCa. HGPIN was first identified in the third decade and increased steadily with age. Latent PCa increased steadily with age with no significant difference in the prevalence between AA and C males in any age group (3rd to 8th decades). HGPIN, on the other hand, was more prevalent in AA men with 18, 31, 69, 78 and 86% in their 4th, 5th, 6th, 7th and 8th decades harboring the lesion. The corresponding figures for C men were 14, 21, 38, 50 and 63% respectively. When HGPIN was quantitated as focal and extensive according to the degree of glandular involvement, extensive HGPIN appeared earlier in AA males under 60 years of age compared to C males cohort. The difference in age distribution appeared to follow a chronological pattern, with HGPIN in AA preceding that of C males by approximately a decade. The second component of this report describes a surgical series of 345 consecutive radical prostatectomies from patients (155 AA and 190 C) with clinically localized PCa, which were thoroughly evaluated microscopically by two urologic pathologists. Similar to the findings in the autopsy study, extensive HGPIN was more prevalent in AA men 60 years of age or younger (57% vs. 33%). In both races, the mean percentage of the gland involved by HGPIN decreased with advancing age in contrast to the mean tumor volume that increased with patient age. These findings indicating a different prevalence of HGPIN in the two racial groups may help explain the higher incidence of prostatic cancer in African-Americans.