Lesions missed on prostate biopsies in cases sent in for consultation

BACKGROUND: There are no reports on how often lesions are missed on prostate needle biopsies. METHODS: Over a 10-month period, 8/99 to 5/00, 3,251 prostate biopsy cases were seen in consultation. RESULTS: We identified 87 (2.7%) patients with missed lesions (n = 9 academic hospitals; n = 44 community hospitals; n = 34 commercial labs). Overall, 119 lesions were missed in 87 patients. Missed lesions were as follows: small atypical glands suspicious for cancer (41 lesions in 35 patients), prostatic adenocarcinoma (39 cancers in 32 patients), high grade prostatic intraepithelial neoplasia (HGPIN) (34 lesions in 30 patients), and HGPIN with adjacent small atypical glands (five lesions in five patients)--some men with more than one type of missed lesion. Detection of the missed lesions would have resulted in either: a definite change in care in 15 of 3,251 (0.5%) patients or a possible change in care (bilateral cancer vs. unilateral cancer; HGPIN vs. atypical) in 17 (0.5%) patients. In 21 (24%) of the cases, the slides were seen by at least two pathologists prior to consultation at our hospital. CONCLUSIONS: Although the number of prostate biopsies with missed lesions in a consult-based population of prostate biopsies appears relatively high (2.7%), the detection of the missed lesions would have only effected a definite change in care in 0.5% of all patients or a possible change in care in another 0.5% of patients. Our data underestimates missed lesions, as the entire specimen was not submitted for review in 41% of cases. Although our incidence of missed lesions gives some indication as to the magnitude of the problem, it cannot be equated with the risk of missing lesions in unselected cases.     

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.     

良性前列腺增生中的高度前列腺上皮内瘤初步观察

本文观察良性前列腺增生（BPH）中的高度前列腺上皮内瘤（HPIN）现象。回顾性分析54例分析耻骨上前列腺摘除术患者的前列腺标本切片。统计其中HPIN的发生率,并结合患者术前PSA值,分别HPIN与非HPIN之间的血PSA值差别。结果发现54例患者中22例有HPIN表现,占总数的40．7％。HPIN组与非HPIN组之间的血PSA值无显著性差异。在本组BPH患者中,HPIN表现占有一定比例,因此认为HPIN现象并非前列腺癌（Pca）专用。本组中HPIN比例偏高与患者平均年龄较大有关。本研究通过血PSA测定尚无法简单区分HPIN和非HPIN。对于HPIN现象,一方面应提高警惕,密切随访;另一方面也不必盲目悲观,毕竟HPIN只是一种前列腺癌的前驱表现,而并不等于同于前列腺癌。     

Predictors of prostate cancer on extended biopsy in patients with high-grade prostatic intraepithelial neoplasia: a multivariate analysis model

OBJECTIVE: To define the importance of extended biopsy in patients with high-grade prostatic intraepithelial neoplasia (HGPIN) and to define predictors of cancer in extended biopsy in patients with HGPIN, using multivariate analysis. PATIENTS AND METHODS: In all, 83 patients with previous sextant biopsy of HGPIN had an extended 11-core biopsy taken. Patients with a negative biopsy for cancer were followed by serum prostate-specific antigen (PSA) and digital rectal examination (DRE) every 6 months. The extended biopsy was repeated in 21 patients. The criteria for second biopsy were an increase in PSA and/or abnormal changes on DRE. Overall, 49 patients had a transurethral resection of the prostate (TURP). The cancer-detection rate on extended biopsy was correlated with risk factors using the chi-square test and multivariate analysis. RESULTS: Extended biopsy detected prostate cancer in 30 of the 83 men (36%), with positive cores in only 20 sextant biopsy sites (67%), in only seven in additional sites (23%), and both in three (10%). Of the 21 patients who had repeat extended biopsy, four (19%) had cancers. There were two carcinomas in the 49 TURP specimens (4%). The PSA level, DRE and transrectal ultrasonography findings were not predictive of cancer in extended biopsies (chi-square test). Patient age, PSA density and the number of cores with HGPIN (all P < 0.001) had a significant effect on the cancer-detection rate, and multivariate analysis showed that all three were independent predictors of cancer. A logistic regression model was designed to predict the probability of cancer in extended biopsy, with an overall accuracy of 78%. CONCLUSION: Extended biopsy improved the cancer detection rate by 23% in patients with HGPIN. Patient age, PSA density and the number of cores with HGPIN were the only independent predictors of cancer.     

Pathological changes of high-grade prostatic intraepithelial neoplasia and prostate cancer after monotherapy with bicalutamide 150 mg

OBJECTIVES:To evaluate the morphological changes induced by a 3-month course of neoadjuvant bicalutamide 150 mg/day before radical prostatectomy (RP) on prostatic adenocarcinoma and high-grade prostatic intraepithelial neoplasia (HGPIN). PATIENTS AND METHODS: In all, 90 patients with cT1-T2 prostate cancer and HGPIN on prostatic biopsy were randomized to receive bicalutamide (150 mg/day for 3 months) before RP, or to have immediate surgery. Surgical specimens were assessed for the histopathological features of cancer, HGPIN and benign epithelium in a blinded manner. The volumes of prostate cancer and HGPIN were evaluated using a stereological (i.e. grid) method. RESULTS: Compared with the bicalutamide-treated group, the ratio of stroma to epithelium, evaluated by visual microscopic assessment in the normal epithelium of the three prostate zones, was significantly lower in the control group, at 2.27 (sd 1.13), than in the treated group, at 1.87 (sd 0.72) (P = 0.048). The mean (sd) tumour volume was significantly lower in the bicalutamide-treated than in the control group, at 0.914 (0.13) vs 1.47 (0.24) mL (P = 0.044). Similarly, the mean (sd) volume of HGPIN was significantly lower in the bicalutamide-treated than in the control group, at 0.34 (0.06) vs 0.62 (0.07) mL (P = 0.003). At RP, specimen Gleason scores in the bicalutamide-treated group were similar to those in the control group, and were no different from the biopsy Gleason scores. CONCLUSIONS: Involution and epithelial shrinkage of prostate cancer and HGPIN were evident after neoadjuvant treatment with bicalutamide 150 mg. There was no evidence of the emergence of higher-grade cancer after treatment.     

Lycopene as a chemopreventive agent in the treatment of high-grade prostate intraepithelial neoplasia

OBJECTIVE: Because of its long latency, slow growing nature, and high prevalence, prostate cancer is the best model for chemoprevention. High-grade prostate intraepithelial neoplasia (HGPIN) is a precursor of prostate cancer. Chemoprevention with lycopene has shown definite results in prostate cancer. We undertook a study to use lycopene as a chemopreventive agent in the treatment of HGPIN for preventing prostate cancer from developing in this vulnerable group of patients. MATERIALS AND METHODS: A total of 40 patients with HGPIN were randomized into 2 groups: one received 4 mg lycopene twice a day for one year, and the other was periodically followed up. Total follow-up was one year. RESULTS: Our results show that lycopene can delay or prevent HGPIN from developing into occult prostate cancer, and there exists an inverse relationship between lycopene and prostate-specific antigen. Being a vegetable carotenoid, lycopene is a safe drug to be used for a longer period without any adverse reaction. CONCLUSION: Lycopene is an effective chemopreventive agent in the treatment of HGPIN, with no toxicity and good patient tolerance.     

DNA quantitation of intraepithelial neoplasia and invasive carcinoma of the prostate

The relation of prostatic intraepithelial neoplasia (PIN) or ductal dysplasia and the development of invasive prostate cancer is not clear. PIN, especially high grade, is usually associated with coexisting invasive cancer. Although some investigators have identified micro foci of invasive cancer evolving from PIN, the two are usually anatomically separated. Because of these distinct anatomic patterns, many investigators have concluded that PIN represents a “field effect” or marker of potential cancer progression, and is not directly involved in or leads to the development of invasive prostate cancer. We measured the DNA content in 49 foci of invasive cancer and 87 foci of PIN identified in 34 radical prostatectomies containing both PIN and invasive cancer. In addition, we examined 13 prostatectomies and 5 TUR specimens containing only PIN. We found that the majority of low grade PIN had normal or diploid range DNA and that approximately half of the high grade PIN were abnormal or aneuploid. Prostates with coexisting diploid range PIN and invasive cancer had an approximately equal number of diploid range and aneuploid invasive cancers. Conversely, almost all of the aneuploid PIN (usually high grade) had coexisting aneuploid invasive cancers. This would support the hypothesis that events in the progression of prostate cancer may be operative in both the development of PIN and invasive cancer. © 1993 Wiley-Liss. Inc.     

Lesions predictive for prostate cancer in a screened population: first and second screening round findings

BACKGROUND: We evaluated the incidence of prostate cancer, high-grade prostatic intraepithelial neoplasia (PIN) and lesions suspicious for prostate cancer (LSPC) in sextant biopsies in two subsequent screening rounds at a 4-year interval and their predictive value for subsequent prostate cancer detection. METHODS: In the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC), 4,117 men underwent sextant biopsy in the 1st screening round. The 2nd round was performed at a 4-year interval and biopsies were taken in 1,840 men. RESULTS: The incidences of prostate cancer, LSPC and PIN in the 1st, respectively 2nd round were 24.6, resp. 19.9% (P = 0.001), 2.7, resp. 2.8% and 0.8, resp. 2.5% (P < 0.0001). Prostate cancer incidence after repeat biopsy for LSPC in the 1st, respectively 2nd round was 36.7 and 17.0%, and after repeat biopsy for PIN 13.3% in both rounds, respectively. Men with a benign biopsy in the 1st round had a significantly lower prostate cancer incidence in the 2nd round compared to men who did not undergo biopsy in the 1st round (10.7 vs. 22.7%, P < 0.0001). CONCLUSIONS: The decrease of prostate cancer detection in the 2nd round was associated with an increase in the incidence of PIN. Strikingly, LSPC diagnosed during the 1st round, but not during the 2nd round were predictive for prostate cancer, while isolated PIN was never predictive for prostate cancer. PIN should not be an indication for repeat biopsy in a screening population. Importantly a 1st round benign biopsy outcome proved to be a negative predictor of subsequent prostate cancer detection.     

Increased spermine oxidase expression in human prostate cancer and prostatic intraepithelial neoplasia tissues

BACKGROUND: Inflammation has been strongly implicated in prostate carcinogenesis, but the precise molecular mechanisms linking inflammation and carcinogenic DNA damage are not known. Induction of the polyamine catabolic enzyme, spermine oxidase (SMO) has been linked to increased reactive oxygen species (ROS) and DNA damage in human gastric and lung epithelial cells and suggest direct mechanistic links between inflammation, SMO activity, ROS production, and epithelial carcinogenesis that are likely relevant in prostate cancer. METHODS: Tissue microarrays consisting of matched normal and diseased specimens from patients diagnosed with prostate cancer, prostatic intraepithelial neoplasia (PIN), or proliferative inflammatory atrophy (PIA), as well as unaffected individuals, were stained for SMO expression and analyzed using image analysis techniques and TMAJ software tools. RESULTS: Average SMO staining was significantly higher in prostate cancer and PIN tissues compared to patient-matched benign tissues. Benign tissues from prostate cancer, PIN, and PIA patients also exhibited significantly higher mean SMO expression versus tissues from prostate disease-free patients. CONCLUSIONS: Tissues from patients diagnosed with prostate cancer and PIN exhibit, on average, locally increased SMO expression in regions of prostatic disease and higher overall SMO expression in prostatic epithelial cells compared to healthy individuals. Further studies are warranted to directly examine the role of SMO-produced ROS in prostate carcinogenesis.