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The prostate gland is unique in that it undergoes rapid regression following castration but regenerates completely once androgens are replaced. Residual ductal components play an important role in the regeneration of a fully functional prostate. In this study, to examine how androgen status affects prostate structure and components, we conducted histopathological studies of the involuted and regenerated mouse dorsolateral prostate (DLP). In the castrated mouse DLP, the number of luminal epithelial cells decreased in a time-dependent manner. On Day 14 postandrogen replacement, the number of luminal epithelial cells was completely restored to the baseline level. In contrast, the number of basal epithelial cells gradually increased in the castrated mouse prostate. The Ki67-labeling index of prostate basal epithelial cells was significantly increased after castration. The number of basal epithelial cells decreased to baseline after androgen replacement. After castration, mRNA expression levels of specific growth factors, such as Fgf2, Fgf7, Hgf, Tgfa, and Tgfb, were relatively abundant in whole mouse DLPs. In organ culture experiments, basal epithelial proliferation was recapitulated in the absence of dihydrotestosterone (DHT). The proliferation of basal epithelial cells in the absence of DHT was suppressed by treatment with an FGF receptor inhibitor (PD173074). Moreover, FGF2 treatment directly stimulated the proliferation of basal epithelial cells. Taken together, these data indicated that the FGF2-FGF receptor signal cascade in the prostate gland may be one of the pathways stimulating the proliferation of basal epithelial cells in the absence of androgens.

Objectives: To investigate the significance of dedicated central pathologic review for Gleason score (GS) correlation between the biopsy and radical prostatectomy (RP) specimens and the prediction of high-grade Gleason patterns. A discrepancy in the GS between the biopsy and RP specimens has been reported., Methods: The Clinicopathological Research Group for Localized Prostate Cancer disease registry collated the data from 1629 patients who had undergone RP from 1997 to 2005. All biopsy and RP specimens were retrospectively re-evaluated by 2 central uropathologists according to the International Society of Urological Pathology consensus. The GS correlation between the biopsy and RP specimens and the presence of high-grade Gleason patterns (4 or 5) were recorded. The GS was categorized into 5 groups (2-4, 5-6, 3 + 4, 4 + 3, and 8-10)., Results: Central review significantly increased the exact concordance rate and decreased the undergrading and overgrading rates between the biopsy and RP specimens compared with local review (P < .05 for all). In each GS or prostate-specific antigen group, the central review biopsy GS had a significantly greater exact concordance rate with the RP specimen GS compared with the local review biopsy GS (P < .05 for all). Regarding high-grade Gleason patterns in the RP specimens, central review showed significantly greater sensitivity, positive predictive value, and negative predictive value than local review (P < .05 for all)., Conclusions: We have demonstrated that central review using the International Society of Urological Pathology consensus improves the GS correlation and better predicts high-grade Gleason patterns compared with local review. We recommend central pathologic review by dedicated uropathologists for multi-institutional studies using data from prostate biopsy and RP specimens., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: The present study was carried out to analyze pathological features of prostatectomy specimens performed at different timing and trigger during active surveillance., Methods: One hundred and thirty-four patients that fit a selection condition similar to the so-called Hopkins' criteria were enrolled into the present study between January 2002 and December 2003. Patients were recommended to start curable treatment when they showed prostate-specific antigen-doubling time of 2 years or shorter or pathological progression at 1-year re-biopsy. Median observation period was 61 months., Results: Fourteen patients underwent radical prostatectomy immediately after enrollment (Group A) whereas 28 patients underwent radical prostatectomy after substantial periods of active surveillance (Group B). Of the 28 Group B, trigger of radical prostatectomy was on protocol in 17 patients (Group B1) whereas 11 patients underwent radical prostatectomy by their preference (Group B2). Upgrade from initial biopsy was observed in 43% of Group A and 68% of Group B. Upgrade was more frequently observed in Group B1 than B2 with border line significance (P = 0.075). Perineural infiltration and positive surgical margin rates of Group B1 were significantly higher than those of B2 (P < 0.05)., Conclusions: Unfavorable pathological features of surgical specimens were more frequently observed in patients who underwent radical prostatectomy due to short prostate-specific antigen-doubling time or biopsy findings than those who underwent radical prostatectomy because of other reasons including patients' preference. Rates of unfavorable pathological features at radical prostatectomy that deviate initial selection criteria was high enough to support integration of frequent biopsies into active surveillance program.

Background: To clarify the pathology of the development of prostatic disorders such as inflammation, cancer, and hyperplasia, we compared histopathological findings of the prostate according to age group., Methods: Whole-mount sections of prostates were used to assess the relationship between age and prostate weight (n=962), prostate histological composition in the transition zone (TZ) and in the peripheral zone (PZ) (n=68), prostate histopathological findings by zone (n=102), and comparison of latent tumor development by age group (n=1,815)., Results: A rapid increase in prostate weight from birth to the 20s was followed by a slow rise thereafter. Volume increases (P<0.01) were observed in all components of glandular epithelium, glandular lumen, and stroma in the TZ from the 40s to 70s inclusive. In the PZ, the epithelial and stromal volumes tended to decrease in an age-dependent manner (P<0.05). Calculi and lymphocyte infiltration were detected at a relatively early age, with a tendency towards an age-dependent increase. Glandular dilation and nodular hyperplasia were noted first in the 30s group, also with a tendency towards age-dependent increase. Latent tumors were first detected in the 30s group (5.6%), and slowly increased thereafter., Conclusions: There was an age-dependent trend towards prostate glandular dilation and prostate enlargement with inflammation. It was demonstrated that tumor and hyperplasia have a long natural history, usually starting in the fourth decade of life, accompanied by dynamic changes with age in glandular tissue composition as well as cell proliferation activity., (Copyright (c) 2005 Wiley-Liss, Inc.)

Objectives: To determine the percent area density of epithelial and stromal components in the development of prostatic hyperplasia in spontaneously hypertensive (SH) rats., Methods: The ventral lobes of prostates obtained from male SH rats and their normotensive counterparts, Wistar Kyoto (WKY) rats, were examined histopathologically at 15, 29, 40, and 54 weeks of age (5 SH and WKY rats each at each age group). The degree of prostatic hyperplasia was evaluated with a score-chart protocol, histoscore. The percent area density of epithelium and stroma of the ventral prostate were determined using a computerized image analysis system., Results: Definite lesions of hyperplastic changes were demonstrated in the ventral prostate of SH rats from 15 to 54 weeks. In comparison with WKY rats, SH rats showed a significantly increased degree of prostatic hyperplasia as reflected by the histoscore values. Furthermore, the histoscore of the ventral prostate of SH rats increased with age (from 21.7 +/- 0.7 at 15 weeks to 26.1 +/- 0.4 at 54 weeks). The percent area density of epithelium and stroma were significantly increased in SH rats, and the ratio of stroma to epithelium ranged from 1:2.94 to 1:3.50 in SH rats but was maintained at 1:1.15 to 1:1.19 in WKY rats during the observation period., Conclusions: The hyperplastic changes of the ventral prostate may develop with advancing age in SH rats. The development of prostatic hyperplasia may result from both epithelial and stromal proliferation and may be predominantly expressed as a glandular type in SH rats.

Purpose: We validated the 2001 Partin tables and developed an original nomogram for Japanese patients using the 2005 International Society of Urological Pathology consensus on Gleason grading. Materials and Methods: Prostatectomy specimens from 1,188 Japanese men who underwent radical prostatectomy for clinically localized prostate cancer (cT1-2) between 1997 and 2005 were analyzed. Polychotomous logistic regression analysis was used to construct a nomogram to predict final pathological stage (organ confined disease, extraprostatic extension, seminal vesicle invasion and lymph node involvement) from 3 variables, including serum prostate specific antigen, clinical stage and biopsy Gleason score. The area under the ROC curve was used to compare the new nomogram with the Partin tables. Results: Preoperative serum prostate specific antigen and biopsy Gleason score were higher in the Japanese cohort than in the Partin cohort. The distribution of clinical and final pathological stages was similar in the 2 cohorts. The AUC for predicting organ confined disease was 0.699 and 0.717 for data applied to the Partin tables and to the new nomogram, respectively. The AUC for predicting lymph node involvement was 0.793 and 0.863, respectively. Conclusions: To our knowledge this is the first preoperative nomogram developed for clinically localized prostate cancer in Japanese patients. Although the new nomogram predicted the pathological stage of prostate cancer in Japanese patients more accurately than the Partin tables, it did not satisfactorily predict organ confined disease. However, other predictive variables, such as more detailed pathological features of biopsy specimens or magnetic resonance imaging, may further improve prediction accuracy. [Copyright &y& Elsevier]

A case of malignant phyllodes tumor of the prostate in a 67-year-old man is reported. The patient was referred to a hospital for urinary retention. From material taken at three transurethral resections of the prostate (TURP), a histological diagnosis of benign prostatic hyperplasia was made. However, at the fourth TURP, phyllodes tumor was diagnosed due to the presence of elongated epithelial ducts and proliferating cellular stroma with mitosis and nuclear atypia. Two months later, total cystoprostatectomy was performed. Histologically, the tumor was composed of dysplastic stromal cells and irregularly elongated epithelial ducts. Five months later the patient developed multiple lung and pelvic lymph node metastases and died. This report documents progression to a higher histological grade of prostatic phyllodes tumor documented with sequential pathological findings obtained from four TURP and surgical specimens over about 3 years. [ABSTRACT FROM AUTHOR]