Presence Of High-grade Prostatic Intraepithelial Neoplasia Research Articles

Clinical features and prognosis of prostate cancer with high-grade prostatic intraepithelial neoplasia.

PurposeTo evaluate the clinical features and biochemical recurrence (BCR) in prostate cancer (PCa) with high-grade prostatic intraepithelial neoplasia (HGPIN).Materials and MethodsWe retrospectively analyzed the medical records of 893 patients who underwent a radical prostatectomy for PCa between 2011 and 2012 at Asan Medical Center; 752 of these patients who did not receive neoadjuvant or adjuvant therapy and were followed up for more than 1 year were included. The cohort was divided into two groups-patients with and without HGPIN-and their characteristics were compared. The Cox proportional hazards model was used to analyze factors affecting BCR.ResultsIn total, 652 study patients (86.7%) had HGPIN. There were no significant differences in preoperative factors between the two groups, including age (p=0.369) and preoperative prostate-specific antigen concentration (p=0.234). Patients with HGPIN had a higher Gleason score (p=0.012), more frequent multiple tumor (p=0.013), and more perineural invasion (p=0.012), but no other postoperative pathologic characteristics were significantly different between the two groups. There were no significant differences in BCR (13.0% vs. 11.5%, p=0.665) and HGPIN was not associated with BCR (p=0.745). In multivariate analysis, only the T stage (p<0.001) was associated with BCR.ConclusionsPCa patients with HGPIN have a higher Gleason score, more frequent multiple tumors, and more perineural invasion than those without HGPIN. The presence of HGPIN is not an independent predictor of BCR.

Clinicopathological analysis of intraductal proliferative lesions of prostate: intraductal carcinoma of prostate, high-grade prostatic intraepithelial neoplasia, and atypical cribriform lesion.

Intraductal carcinoma of the prostate (IDC-P) and high-grade prostatic intraepithelial neoplasia (HGPIN) are two distinct intraductal lesions; the former is usually associated with invasive carcinoma and has an aggressive course while the latter is considered a precancerous lesion. In addition, there are morphologically lesions not well characterized that fall between IDC-P and HGPIN, consequently termed "atypical cribriform lesions (ACLs)." Using whole mount radical prostatectomy specimens, we evaluated the relationship between these intraductal proliferative lesions and clinicopathological parameters. In this study, ACLs were characterized as a loose cribriform intraductal proliferation with greater architectural complexity when compared to HGPIN, but lacking significant nuclear pleomorphism and/or comedonecrosis. Of 901 radical prostatectomies (2006-2012), IDC-P, ACL, and HGPIN were recorded in 155, 22, 436 cases, respectively. Patients with IDC-P showed more aggressive pathologic features when compared to HGPIN. Invasive cancers in patients with ACL had higher Gleason score (P=.00016), larger tumor volume (P=.025), and more advanced pT stage (P=.023) than those with HGPIN. Cases with ACL showed a higher risk of biochemical recurrence than those with HGPIN and a lower risk than those with IDC-P based on log-rank tests (P=.0045 and P=.0069, respectively). In multivariate analysis, the presence of HGPIN was identified as an independent predictor for infrequent biochemical recurrence (P=.0058). We confirmed IDC-P as a marker of adverse pathologic features and clinical aggressiveness. Our results suggest that ACL should be distinguished from HGPIN and these lesions mandate active clinical surveillance.

Concomitant High-Grade Prostatic Intraepithelial Neoplasia Is Associated with Good Prognosis Factors and Oncologic Outcome after Radical Prostatectomy

Objectives: To assess correlations between concomitant high-grade prostatic intraepithelial neoplasia (HGPIN), pathological features and oncologic outcomes after radical prostatectomy (RP). Material and Methods: We prospectively collected a single-institution database of 2,351 patients who underwent RP between 1998 and 2011. Results: 1,272 (54.1%) patients had HGPIN on specimens. The mean follow-up was 28 months. Presence of HGPIN was significantly associated with a favorable preoperative risk status and with pathological factors of poor prognosis in RP specimens. Patients without HGPIN had a worse biochemical recurrence-free survival compared with those with HGPIN in RP specimen (log-rank test: p = 0.015). The 3-year RFS rate was 73.9% for the HGPIN group versus 67.2%. The absence of HGPIN was also significantly correlated with the use of androgen deprivation treatment during the follow-up (p < 0.001). In Cox multivariate analysis, taking into account the other prognostic pathological factors, HGPIN was not an independent predictive factor for PSA failure (p = 0.868). Conclusion: HGPIN is associated with factors of good prognosis but fails to show independent significance when classical pathological prognostic factors are taken into account.

245 SHOULD STAGING TRANSRECTAL SATURATION BIOPSY BE A STANDARD FOR ASSESSMENT OF DISEASE PROGRESSION & FOLLOW UP FOR PROSTATE CANCER PATIENTS ON ACTIVE SURVEILLANCE?

INTRODUCTION AND OBJECTIVES: Prostate cancer (PCa) aggressiveness assessment is mandatory to determine the appropriateness for Active surveillance (AS). Our objective is to assess the accuracy of staging saturation prostate biopsy (SB) compared to extended prostate biopsy (EB) in patients on AS protocol. METHODS: From IRB approved database we reviewed 485 biopsies from 383 patients diagnosed with PCa on AS protocol from 2000-2011. Gleason sum ,total gland volume ,number of positive cores, maximum cancer % per core, prostate specific antigen (PSA) at time of the biopsy, % free PSA ,high grade prostatic intraepithelial neoplasia(HGPIN) and atypical small acinar cell proliferation (ASAP) were assessed as predictors of cancer progression. We compared the ability of each template to identify Gleason 7 diseases, 2 core involvement and 50% cancer involvement in each core. RESULTS: Among 485 biopsies ,288 were EB (8-14 cores) and 197 were SB( 20 cores) .Our univariate analysis showed that the “recategorization” identified with SB is greater as evidence by gleason 7 disease (p 0.0004) and 2 core involvement (p 0.002) . We also found that the presence of HGPIN (p 0.03) and PSA at time of the biopsy (p 0.02) were statistically significant compared to EB (table 1). Moreover multivariate analysis showed that SB identified higher Gleason ( 7) disease (p 0.04) and number of positive cores ( 2 cores) (p 0.02). (Table 2). CONCLUSIONS: Staging SB identifies more accurately PCa progression in patients electing AS for their low grade, low volume PCa compared to EB. We recommend using SB ( 20 cores) as a standard protocol for patients on AS.

In situ and intraductal epithelial proliferations of prostate: definitions and treatment implications

• High-grade prostatic intraepithelial neoplasia (HGPIN) is an intracellular proliferation of ductal epithelial cells. On its own, the presence of HGPIN does not warrant active intervention. • In contrast, intraductal carcinoma of prostate and prostatic ductal adenocarcinoma of prostate are markers of aggressive prostatic adenocarcinoma. • The presence of even small foci of these tumours on biopsy warrants immediate intervention, even in the absence of demonstrable invasive disease. • This second part of the review of in situ epithelial proliferations of the prostate looks at these conditions in more detail.

High grade prostatic intraepithelial neoplasia does not display loss of heterozygosity at the mutation locus in BRCA2 mutation carriers with aggressive prostate cancer

What's known on the subject? and What does the study add? The risk of developing aggressive prostate cancer is increased for men carrying a pathogenic germline mutation in BRCA2. An earlier study by the Kathleen Cuningham Consortium for Research into Familial Breast Cancer showed that BRCA2 mutation carriers displayed a loss of heterozygosity (LOH) within their prostate cancer tissue in the majority of cases, thus implying that the prostate cancer in these men occurred as a result of LOH for BRCA2. High grade prostatic intraepithelial neoplasia (HGPIN) has been considered a precursor to prostate adenocarcinoma in some, but not all, cases of prostate adenocarcinoma. The study found that there was no LOH for BRCA2 in HGPIN. From this small cohort of BRCA2-positive men, we suggest HGPIN is not necessarily a precursor to their prostate cancer development. The presence of HGPIN in a TRUS biopsy in these men at risk of high risk disease is not an indication for prostatectomy. • To determine if high grade prostatic intraepithelial neoplasia (HGPIN), which is considered a precursor to the development of prostate adenocarcinoma, displays the same genetic hallmarks as adenocarcinoma. • To identify, using molecular genetic techniques, if HGPIN is a precursor of tumour development and progression in men carrying a pathogenic germline mutation in BRCA2. • Ten participants from the Kathleen Cuningham Consortium for Research into Familial Breast Cancer cohort of high-risk breast cancer families were identified, with (i) a diagnosis of aggressive prostate cancer and presence of HGPIN, (ii) a pathogenic BRCA2 mutation, and (iii) access to archival prostate tissue specimens. • Loss of heterozygosity (LOH) at the BRCA2 gene was examined using mutation-specific PCR and sequencing of DNA from laser microdissected HGPIN. • Within this cohort of 10 pathogenic BRCA2 carriers, no patient displayed LOH at the mutation locus within HGPIN, irrespective of whether or not corresponding adenocarcinoma DNA displayed LOH. • Although HGPIN is considered a precursor to cancer, as no LOH was observed, this assay does not provide a genetic marker that may be considered a positive predictor of tumorigenesis in BRCA2 carriers. • In this group of high-risk men, early screening via prostate-specific antigen testing, rectal examination and prostate biopsy may be prudent to permit the detection and the optimum clinical management of prostate cancer.

High grade intraepithelial neoplasia of prostate is associated with values of prostate specific antigen related parameters intermediate between prostate cancer and normal levels

High grade prostatic intraepithelial neoplasia (HGPIN) is widely regarded as the precancerous. The aim of this study was to determine PSA related parameters in patients with initial PSA values 2-10 ng/mL and diagnosis of HGPIN without finding carcinoma at the time of their first needle biopsy. Study groups consisted of 100 men who were diagnosed HGPIN, 84 with cancer and 183 with benign hyperplasia on first biopsy of prostate. Total PSA and free PSA were measured and ratio free/total PSA and PSA density calculated. Mean values of these parameters were compared, and receiver operating characteristic curves were used for comparison of PSA related parameters to discriminate groups of patients.Total PSA, free PSA level and PSA density in patients with HGPIN (6.388 ng/mL) did not differ significantly compared to prostate carcinoma (6.976 ng/mL) or benign prostatic hyperplasia (6.07 ng/mL) patients. Patients with HGPIN had significantly higher ratio free/total PSA than those with prostate carcinoma (0.168 vs 0.133), but significantly lower than patients with benign prostatic hyperplasia (0.168 vs 0.185). Ratio of free/total PSA significantly discriminate HGPIN from prostate carcinoma with sensitivity 84.52 and specify 45.00 at cut-off point of ≤ 0.18. Values of PSA, free PSA and ratio free/total PSA in cases of HGPIN appear to be intermediate between prostate cancer and normal levels. Ratio of free/total PSA may help in decision to repeat biopsies in the presence of HGPIN on biopsy, without concomitant prostate cancer, in patients suitable for curative treatment, with normal digito-rectal examination and trans-rectal sonography.

High-grade prostatic intraepithelial neoplasia and atypical small acinar proliferation on initial 21-core extended biopsy scheme: incidence and implications for patient care and surveillance

To evaluate the incidence of high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP) in an initial 21-core extended biopsy scheme and to determine the prostate cancer detection rate in the repeated biopsy. Between 2002 and 2008, 2,006 patients underwent a first 21-core extended biopsy scheme. Incidences of cancer, ASAP and HGPIN were studied. Cancer detection rate in the repeated 21-core extended biopsy for ASAP and HGPIN was reported and compared with those obtained on repeated biopsy for clinico-biological indications. Incidences of HGPIN and ASAP were 1.7 and 1.1%, respectively. The 6-core and 12-core biopsy schemes detecting HGPIN would have missed the diagnosis of cancer in 10 and 3.6% of cases, compared to a 21-core biopsy protocol, respectively. The cancer detection rate on repeated biopsy for HGPIN was 19% and not significantly different compared with the detection rate on repeated biopsy for clinico-biological indications (16.8%, p = 0.77). Seven prostate cancers were found among the 17 re-biopsies for ASAP revealing a detection rate of 41.2% (p = 0.01). All detected cancers were organ confined. No clinico-pathological data were independent predictor of cancer on repeated biopsy. Our report demonstrates the different risk profiles for HGPIN and ASAP in a 21-core extended biopsy scheme. The presence of HGPIN does not imply a higher risk for cancer detection at immediate re-biopsy compared to other patients for whom repeated biopsies were indicated for increasing or persistently increased PSA levels. Repeated biopsy is warranted when ASAP is diagnosed because of a high risk of prostate cancer.

Prevalence of High-Grade Prostatic Intraepithelial Neoplasia in Prostate Gland of Korean Men: Comparisons Between Radical Prostatectomy and Cystoprostatectomy

Objectives To evaluate the prevalence of high-grade prostatic intraepithelial neoplasia (HGPIN) and its association with prostate cancer in Korean men. Methods A total of 160 patients who underwent radical prostatectomy for clinical prostate cancer were included as study subjects and 29 patients who underwent radical cystoprostatectomy for muscle-invasive bladder cancer were included as controls. Each intact prostate gland was serially sectioned at 3-mm intervals perpendicular to the posterior surface. The presence and prevalence of prostate cancer and HGPIN were assessed and their association evaluated. Results High-grade prostatic intraepithelial neoplasia was present in 81 (70.4%) of 115 patients who underwent radical prostatectomy and in 8 (27.6%) of 29 patients who underwent cystoprostatectomy. This difference was statistically significant ( P <0.001). Among the patients who underwent cystoprostatectomy, HGPIN was present in 5 (33.3%) of 15 patients with prostate cancer and in 3 (21.4%) of 14 patients with no evidence of prostate cancer. The presence of HGPIN had no correlation with prostate-specific antigen level, disease stage, tumor volume, grade, lymphovascular invasion, or surgical margin status. Conclusions The prevalence of HGPIN in Korean men with clinical prostate cancer was as great as that of Western men. Previous studies, and our results, had demonstrated a lower prevalence of HGPIN in Asian men who underwent cystoprostatectomy. The different prevalence of HGPIN found in incidental prostate cancer, between Asian and Western men, suggests that factors could be preventing the progression of prostate cancer or different characteristics of the prostate cancer in Asian populations.

Evaluating high-grade prostatic intraepithelial neoplasia as a predictor of outcome following radical prostatectomy

4612 Background: The presence of high-grade prostatic intraepithelial neoplasia (HGPIN) has been associated with future development of prostate cancer. High-grade intraepithelial neoplasia in other malignancies is associated with adverse outcome. This study examines the relationship between the presence of HGPIN in prostatectomy specimens, biochemical disease free survival (bDFS) and other cancer specific outcomes following radical retropubic prostatectomy (RRP). Methods: The Columbia University Urologic Oncology Database was reviewed and 2,522 were identified who had undergone radical prostatectomy from 1988 to 2005; 2,133 patients with or without HGPIN were included. Two-sample proportion analysis of means with 95% confidence intervals and ANOVA techniques were used to evaluate the relationship between HGPIN and pathologic stage, Gleason sum, perineural invasion, multifocality, extracapsular extension (ECE), margin status, and nodal status. Kaplan-Meier analysis with log-rank test and a multivariate Cox proportional hazard model controlling for preoperative PSA, Gleason sum and pathologic stage were used to assess differences in bDFS. Results: 1,885 of 2,133 (88.4%) patients demonstrated HGPIN. There was no significant difference in the distribution of pathologic stage or Gleason sum between the patients with and without HGPIN. The HGPIN-positive group had higher rates of perineural invasion (69.9 vs. 57.5%; p = 0.003), multifocality (63.0 vs. 38.4%; p = 0.000) and ECE (56.4% vs. 48.4%; p = 0.059). There was no statistically significant difference observed in nodal status or margin status between the two groups. Patients without HGPIN had an increased bDFS demonstrated by a predicted disease free survival of 73.6% versus 67.0% at 9 years (p = 0.045) with a median follow-up of 50 months. In the multivariate Cox hazard model HGPIN, PSA, Gleason sum and pathologic stage were validated as independent predictors of failure (p &lt; 0.001). The risk of failure was 1.9 × greater in the HGPIN-positive group than the HGPIN-negative group (p=0.006). Conclusions: The presence of HGPIN in the radical prostatectomy specimen denotes a significantly higher rate of tumor multifocality, perineural invasion, ECE, and ultimately biochemical recurrence. No significant financial relationships to disclose.

Recursive partitioning for risk stratification in men undergoing repeat prostate biopsies

The current study was performed to identify risk factors and risk groups for carcinoma detection in men undergoing repeat prostate biopsies. The medical records of all men who had a negative initial prostate biopsy and underwent at least one repeat biopsy between 1992 and 2003 were reviewed to extract age, race, family history of prostate carcinoma, body mass index, referral indication, all prostate-specific antigen (PSA) values, digital rectal examination, PSA density (PSAD), the presence of a hypoechoic lesion, and the presence of high-grade prostatic intraepithelial neoplasia (HGPIN) on initial biopsy. Risk factors for a subsequent diagnosis of prostate carcinoma were identified using the log-rank test and a stepwise, stratified Cox regression model. Based on the risk factors identified by Cox regression analysis, recursive partitioning was further used for risk stratification. A total of 373 patients underwent 975 biopsy procedures. During a median follow-up of 37.0 months, prostate carcinoma was detected in 107 of 373 patients (28.9%). Independent predictors of a positive biopsy (P < 0.05) were PSA doubling time (PSADT), PSAD, referral indication, the presence of HGPIN, patient age, and family history of prostate carcinoma. Recursive partitioning identified 4 distinct risk groups that were characterized by their PSADT and PSAD and the presence of HGPIN and had estimated 2-year and 5-year carcinoma detection rates of 3 +/- 1% and 21 +/- 4%, 28 +/- 5% and 40 +/- 7%, 22 +/- 6% and 58 +/- 8%, and 66 +/- 9% and 100%, respectively. The authors identified a series of independent risk factors for prostate carcinoma detection after an initial negative prostate biopsy and characterized clinically meaningful and distinct patient risk groups. Despite a negative initial biopsy, patients with high-risk features remain at risk for the detection of prostate carcinoma.

Serum Insulin-Like Growth Factor-I Levels and Prostatic Intraepithelial Neoplasia: A Clue to the Relationship Between IGF-I Physiology and Prostate Cancer Risk

Serum insulin-like growth factor-I (IGF-I) levels at the higher end of the reference range have been associated with increased risk for the future development of prostate cancer. We determined whether high serum IGF-I levels are associated with precancerous lesions of the prostate. We conducted a case-control study to determine whether high serum IGF-I levels were associated with the presence of high-grade prostatic intraepithelial neoplasia (HGPIN) among patients who presented for prostate biopsy because of an abnormal serum prostate-specific antigen level or digital rectal exam. We measured serum IGF-I and insulin-like growth factor binding protein-3 (IGFBP-3) prior to prostate biopsy and compared them between 103 men with HGPIN (cases) and 205 men with normal prostate histology (controls). The mean IGF-I level in patients with HGPIN (130.2 ng/mL) was significantly higher compared with controls (118.8 ng/mL, P = 0.01). The mean IGFBP-3 level in patients with HGPIN (2,393.9 ng/mL) was also higher compared with controls (2,276.0 ng/mL, P = 0.06). After adjusting for age, prostate-specific antigen, digital rectal examination, and ethnic background, the odds ratio for a HGPIN diagnosis among men in the highest relative to the lowest quartile of serum IGF-I level was 1.94 (95% confidence interval, 1.0-3.7; P = 0.04). The potential association between a high serum IGF-I level and the presence of HGPIN may represent an important clue to understanding the basis for the relationship between IGF-I physiology and prostate cancer risk. Larger studies will be required to confirm this relationship.

Should High-Grade Prostatic Intraepithelial Neoplasia Change Our Approach to Infravesical Obstruction?

Objectives: To investigate whether coexistence of high-grade prostatic intraepithelial neoplasia (HPIN) should change our therapeutic approach to infravesical obstruction. Material and Methods: Of 505 patients who underwent sextant transrectal ultrasonography (TRUS)-guided prostate biopsy, 65 (12.8%) had HPIN and 29 of them underwent prostatectomy (23 transurethral resection of prostate (TURP), 6 open) due to obstructive urinary symptoms. Patients without carcinoma were followed up with semiannual prostate-specific antigen (PSA) and digital rectal examination. After a follow-up of 24.8 ± 11.0 months, 19 of 29 patients who accepted our call had another sextant biopsy. Results: Mean age and initial mean PSA values of 29 patients were 67.6 ± 6.7 years and 9.26 ± 5.91 ng/ml, respectively. The final pathological evaluation of the surgical specimens revealed 2 prostatic adenocarcinomas both in the TURP group. The remaining 27 (93.2%) patients were found to have benign prostatic hyperplasia (BPH) and their serum PSA levels declined from 9.26 ± 5.91 to 4.59 ± 2.0 ng/ml 3 months after prostatectomy. Of the 19 patients who had another biopsy with a mean PSA value of 4.06 ± 4.61 ng/ml, 15 and 4 of them had BPH and HPIN respectively. Conclusions: Our preliminary data indicate that the presence of HPIN on TRUS-guided biopsies is not a factor to delay an indicated surgical intervention for infravesical obstruction.

High-grade prostatic intraepithelial neoplasia in needle biopsy as risk factor for detection of adenocarcinoma: Current level of risk in screening population

Objectives To assess the current incidence of prostate carcinoma detection in serial biopsies in a prostate-specific antigen-based screening population after a diagnosis of isolated high-grade prostatic intraepithelial neoplasia (HG-PIN) in needle biopsy tissue. Methods We retrospectively identified 190 men with a diagnosis of isolated HG-PIN in needle biopsy tissue. Most men (86%) were diagnosed from 1996 to 2000. Logistic regression analysis was used to predict the presence of carcinoma in these 190 men and in a control group of 1677 men with only benign prostatic tissue in needle biopsy tissue. Results The cumulative risk of detection of carcinoma on serial sextant follow-up biopsies was 30.5% for those with isolated HG-PIN compared with 26.2% for the control group ( P = 0.2). Patient age ( P = 0.03) and serum prostate-specific antigen level ( P = 0.02) were significantly linked to the risk of cancer detection, but suspicious digital rectal examination findings ( P = 0.1), the presence of HG-PIN ( P = 0.2), and the histologic attributes of PIN were not (all with nonsignificant P values). HG-PIN found on the first repeat biopsy was associated with a 41% risk of subsequent detection of carcinoma compared with an 18% risk if benign prostatic tissue was found on the first repeat biopsy ( P = 0.01). Conclusions The results of our study have shown that the current level of risk for the detection of prostate carcinoma in a screened population is 30.5% after a diagnosis of isolated HG-PIN in a needle biopsy. This risk level is lower than the previously reported risk of 33% to 50%. HG-PIN is a risk factor for carcinoma detection only when found on consecutive sextant biopsies. The data presented here should prompt reconsideration of repeat biopsy strategies for HG-PIN, and re-evaluation of the absolute necessity of repeat biopsy for all patients with HG-PIN.

Can the number of cores with high-grade prostate intraepithelial neoplasia predict cancer in men who undergo repeat biopsy?

Objectives To evaluate whether the presence of, or the number of cores containing, high-grade prostatic intraepithelial neoplasia (PIN) found in men who underwent initial extended multisite biopsy could predict which men would have prostate cancer on subsequent repeat biopsies. Methods Between June 1997 and January 2003, 1086 men underwent initial prostate biopsy for early detection of prostate cancer using an extended multisite biopsy scheme. Of these, 175 men without cancer underwent at least one repeat biopsy (range one to three; median interval between biopsies, 3 months). Among these 175 patients, 47 had high-grade PIN on initial biopsy. Results The initial extended biopsy identified cancer in 33.8% (367 of 1086) and high-grade PIN in 20.8% (226 of 1086). The incidence of high-grade PIN only in patients found to have cancer on initial biopsy was 29.7% (109 of 367). The presence of high-grade PIN was associated with concurrent prostate cancer at the initial biopsy ( P <0.0001). Overall, repeat biopsy identified cancer in 18.3% of the 175 men. Of the 47 men with high-grade PIN, 5 (10.6%) were found to have cancer on repeat biopsy. The number of biopsy specimens positive for high-grade PIN on initial biopsy was not associated with the likelihood of prostate cancer on repeat biopsy. Multivariate logistic regression analysis showed that neither the presence of high-grade PIN nor the number of cores containing high-grade PIN on initial biopsy were predictors for prostate cancer on repeat biopsy. Conclusions The number of cores positive for high-grade PIN was not predictive for cancer on repeat biopsy.

Significance of high-grade prostatic intraepithelial neoplasia in needle biopsy specimens

Objectives. To examine the significance of high-grade prostatic intraepithelial neoplasia (HGPIN) in biopsy specimens. Methods. We performed sextant biopsies on a series of 83 cystoprostatectomy specimens removed for bladder cancer. For each case the number of foci and volume of both HGPIN and prostate cancer were assessed in the prostatectomy specimens and compared with the number of biopsy specimens involved by HGPIN. Results. We identified HGPIN in 82 (99%) of 83 prostatic glands, whereas prostate cancer was found in 41 cases (49%). Corresponding sextant biopsies harbored both HGPIN and prostate cancer in 6 cases (7%), whereas only HGPIN was diagnosed in 29 sextant biopsies (35%). There was a positive correlation between the number of biopsy specimens containing HGPIN and the volume and multifocality of HGPIN in the corresponding prostatic glands. Prostates with HGPIN on sextant biopsy contained prostate cancer significantly more often when compared to cases with no HGPIN on sextant biopsy. Frequency of concurrent prostate cancer was higher in cases with two or more biopsy specimens containing HGPIN than in cases with only one such biopsy specimen, but case numbers of these categories were too small to render this difference statistically significant. Conclusions. The presence of HGPIN in sextant biopsies is a significant predictor of concurrent prostate cancer. Multifocality of HGPIN is a useful parameter in assessing the extent of HGPIN in the corresponding prostates. Its value in predicting a significantly increased risk of concurrent prostate cancer needs to be further investigated in larger case studies.

Clinical Management of Premalignant Lesions of the Prostate

AbstractThe presence of high-grade prostatic intraepithelial neoplasia (PIN) in a prostate biopsy is a considerable risk factor for the presence of prostate cancer, with up to 73% of patients having cancer on rebiopsy. The risk is related to the clinical setting (screening vs urological practice) and patient factors such as prostatic serum antigen (PSA) and findings on digital rectal examination (DRE). Thus, high-grade PIN has serious clinical implications. The aim of this paper is to propose practical guidelines for the clinical management of PIN. Based on current knowledge we recommend that: Only patients considered for curative treatment of prostate cancer be further investigated for a PIN biopsy finding. A palpable nodule or tumor-suspicious transrectal ultrasonography (TRUS) finding, in conjunction with a finding of high-grade PIN on prostate biopsy, should prompt rebiopsy. An elevated PSA level or an elevated PSA density should also warrant repeat biopsy, as the most likely cause of PSA elevation is concomitant prostate cancer. The presence of high-grade PIN on biopsy without concomitant prostate cancer in patients suitable for curative treatment, notwithstanding normal DRE, TRUS or PSA, should prompt repeat biopsies, as the association with prostate cancer is significant. The presence of PIN alone on biopsy does not warrant treatment, as a substantial number of rebiopsies yield only PIN.

Influence of high-grade prostatic intra-epithelial neoplasia on total and percentage free serum prostatic specific antigen.

To analyse the influence of high-grade prostatic intra-epithelial neoplasia (HGPIN) on total and percentage free serum prostatic specific antigen (PSA). The total and free serum PSA levels were measured (using a double-monoclonal antibody immunoassay, Tandem and Tandem free PSA, Hybritech Inc, Liège, Belgium) in 570 consecutive patients undergoing sextant ultrasound-guided prostatic biopsy because of an abnormal digital rectal examination or a serum PSA concentration of > 4.0 ng/mL. The main diagnosis was benign disease in 321 (56%) and prostate cancer in 249 (44%). HGPIN was detected in 85 (15%) of the patients; in 17 (20%) it was associated with benign tissue and in 68 (80%) with prostate cancer. Patients with benign disease had a median total serum PSA level of 7.2 with no HGPIN and 7.7 ng/mL when HGPIN was present (P>0.05); the corresponding values in patients with prostate cancer were 16.0 and 15.9 ng/mL (P>0.05). The median percentage free serum PSA was 15.8 in patients with HGPIN-free benign disease and 14.1 when HGPIN was present (P>0.05); the corresponding values in patients with prostate cancer were 9.7 and 11.0 (P>0.05). In a multivariate analysis, prostate cancer was the major contributor to total and percentage free serum PSA levels. The presence of HGPIN does not contribute significantly to total and percentage free serum PSA levels.

Immunoreactive p53 Protein in High-Grade Prostatic Intraepithelial Neoplasia

p53 protein accumulation in the nuclei of prostatic carcinoma cells, as detected by immunohistochemistry, has been associated with increased cell proliferation rate, increased histologic grade and stage, androgen independence and decreased patient survival. Little is known, however, of p53 in prostatic intraepithelial neoplasia (PIN), the putative precursor proliferation for moderately to poorly differentiated peripheral zone carcinoma of the prostate. In this investigation, we utilized a panel of antibodies reactive with p53 protein to assess p53 protein accumulation in prostatic epithelial hyperplasia, PIN and prostatic carcinoma. Forty patients who had undergone radical prostatectomy were selected for study based on the presence of high grade PIN and carcinoma in the same prostate tissue block. Tissue sections were treated with microwave irradiation for antigen retrieval, and antibodies DO-7, PAb1801 and CM-1 were used for immunohistochemical analysis. An intense signal for immunoreactive p53 was identified in the nuclei of 7/40 (17.5%) clinically-localized prostatic carcinomas. In all 7 cases, high grade PIN also exhibited intense p53 immunoreactivity, whereas only one case of hyperplasia contained immunoreactive p53 protein. These findings support a close relationship between high grade PIN and carcinoma in a subset of primary prostatic carcinomas with high-level p53 protein accumulation.