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Jonathan I Epstein

Publications and source records attributed to Jonathan I Epstein.

At least 109 records · Page 6Linked to original sources
PubMed2004

Quantitative GSTP1 methylation levels correlate with Gleason grade and tumor volume in prostate needle biopsies.

PURPOSE: Methylation of the GSTP1 gene promoter region is the most common epigenetic change in prostate cancer. The quantitative GSTP1 methylation assay, a recently developed methylation specific and polymerase chain reaction based technique, allows the accurate discrimination of benign prostate tissue and prostate cancer even in small, formalin fixed prostate needle biopsies. In this study we investigated whether GSTP1 methylation correlated with Gleason grade and tumor volume in prostate biopsies. We also compared quantitative GSTP1 methylation with the histological diagnosis in each biopsy. MATERIALS AND METHODS: Formalin fixed, paraffin embedded prostate needle cores (25 mu) were used for the GSTP1 methylation study. After excluding 98 prostate needle cores (47%) with insufficiently extracted DNA 109 biopsies from 40 patients with prostate cancer of various Gleason grades and tumor volume, and benign prostate tissue were tested for GSTP1 methylation using quantitative fluorogenic real-time methylation specific polymerase chain reaction. RESULTS: A total of 13 benign and 96 cancer biopsy parts were included in this study. GSTP1 methylation was positive (GSTP1-to-ACTB ratio 5 or greater) in 83 of 96 cancer parts (86.5%). All 13 benign parts (100%) were negative for GSTP1 methylation with a methylation level of 0 in 12 and 1 in 1. The sensitivity and specificity of quantitative GSTP1 methylation assay were 86.5% and 100%, respectively. Quantitative GSTP1 methylation correlated with Gleason grade, demonstrating higher GSTP1 methylation in higher Gleason grade tumors (Spearman correlation coefficient 0.377, p < 0.0001). Likewise, GSTP1 methylation also correlated with the cancer percent per biopsy (Spearman correlation coefficient 0.567, p < 0.0001). A multiple linear regression model predicted the greater contribution of cancer percent than Gleason grade to quantitative GSTP1 methylation levels. CONCLUSIONS: We confirmed that the quantitative GSTP1 methylation assay reliably discriminates benign and malignant prostate tissues, thus, augmenting the routine histological evaluation of prostate needle biopsies. In addition, quantitative GSTP1 methylation also correlated with prostate cancer Gleason grade and cancer volume, suggesting that quantitative GSTP1 methylation may be of prognostic significance.

Acyltransferases↗
PubMed2004

Prostate specific antigen progression in men with lymph node metastases following radical prostatectomy: results of long-term followup.

PURPOSE: We examined the clinical outcome of patients with lymph node metastases found at prostatectomy with the goal to identify factors that predict freedom from prostate specific antigen (PSA) progression. MATERIALS AND METHODS: We retrospectively reviewed the records of 3,264 consecutive men with clinically localized prostate cancer who underwent extended pelvic lymphadenectomy and radical prostatectomy performed by a single surgeon between April 1982 and March 2003. Patients with pathologically confirmed lymph node metastases and no history of adjuvant treatment were identified. Clinical and histopathological factors were analyzed for an association with time to PSA progression using univariate and multivariable analyses. RESULTS: Of the 143 patients (4.4% of total) in the study with nodal involvement 24 (16.8%) were free of disease at last followup (median 6 years). Median time to failure was 2 years with PSA progression occurring as late as 11 years postoperatively in 2 patients. The 5 and 7-year PSA progression free rate in all lymph node positive patients was 26.5% and 10.9%, respectively. A 15% or greater incidence of positive nodes (p = 0.0008) and high prostatectomy Gleason score (ie score 8 to 10, p = 0.008) were independent predictors of PSA progression in multivariate Cox proportional hazards models. Seminal vesicle invasion (HR 1.45, p = 0.063) or positive surgical margins (HR 1.43, p = 0.063) were marginally significant in the multivariate model. The 5-year PSA progression-free rate was 52% in men with less than 15% positive lymph nodes, prostatectomy Gleason score 7 or less and negative seminal vesicle invasion. CONCLUSIONS: While the incidence of lymph node positive disease in patients undergoing radical prostatectomy is infrequent in the PSA era, patients with nodal involvement may experience disease progression as remote as 1 decade after surgery. Pathological factors such as the percent of positive lymph nodes, prostatectomy Gleason score and seminal vesicle invasion appear to predict an increased risk of PSA failure in this population.

Disease Progression↗
PubMed2004

Impact of surgical delay on long-term cancer control for clinically localized prostate cancer.

PURPOSE: Radical retropubic prostatectomy (RRP) as definitive management for clinically localized prostate cancer is commonly performed within months of diagnosis. Despite patient anxiety there is little evidence to suggest that a delay of several months from diagnosis to RRP is associated with a worse cancer control rate. However, a recent study cast doubt on the safety of such a delay with respect to cancer control. Therefore, in a contemporary series we determined long-term cancer control in men who underwent RRP for clinically localized prostate cancer with some treated early and others treated after a longer delay. MATERIALS AND METHODS: We analyzed data on 926 men who underwent RRP between January 1989 and December 1994. Age, preoperative serum prostate specific antigen (PSA), biopsy Gleason score, clinical and pathological stage, and biochemical recurrence were compared between 162 men who underwent RRP 60 days or less from biopsy and 764 who underwent RRP after a greater delay. Disease-free (PSA less than 0.2 ng/ml) survival rates were compared using Kaplan-Meier analysis. Pathological staging was compared using logistic regression. RESULTS: The different groups were well matched for age, serum PSA, pathological stage and followup. However, significantly more men who underwent RRP between 121 and 150 days, and 151 days or greater had T1c disease (48% and 57% vs 35%, p<0.04 and <0.0001, respectively). In addition, significantly more men operated on at 151 days or greater had biopsy Gleason scores 2 to 6 (86% vs 65%, p<0.0001) and significantly fewer had Gleason score 7 disease (13% vs 30%, p<0.002). Men who underwent RRP after 60 or less days had 5 and 10-year biochemical disease-free survival rates comparable to those in men who underwent RRP after 61 to 90, 91 to 120 and 121 to 150 days after diagnosis (82% and 78%, 86% and 78%, 86% and 75%, and 86% and 82%, respectively). Those operated on at 151 days or greater had significantly greater 5 and 10-year biochemical disease-free survival rates (89% and 87%, p<0.04). However, when patients were stratified into different subgroups based on clinical stage, serum PSA and biopsy Gleason score a delay of 150 days or greater no longer impacted differently on long-term cancer control rates. CONCLUSIONS: Delays of up to several months from prostate cancer diagnosis to RRP do not appear to impact long-term biochemical cancer control rates. Therefore, patients can be reassured that there is no immediate urgency to perform RRP after prostate cancer diagnosis, especially in those with T1c disease and biopsy Gleason scores less than 7.

Adenocarcinoma↗
PubMed2003

Quantitative alterations in nuclear structure predict prostate carcinoma distant metastasis and death in men with biochemical recurrence after radical prostatectomy.

BACKGROUND: Microscopic histologic grade has been the best predictor of prostate carcinoma (PCa) progression in men after surgical therapy. The ability to predict accurately, at the time of surgery, which patients are likely to develop metastatic PCa would enable optimization of disease management with adjuvant therapy. The authors assessed the ability of pathologic, nuclear morphometric, and chromatin parameters to predict metastatic PCa progression and/or death in 227 men with biochemical recurrence and long-term follow-up after undergoing radical prostatectomy. METHODS: Multivariate logistic regression (LR) was used to calculate quantitative nuclear grade (QNG) solutions using the variances of 60 nuclear morphometric descriptors (NMDs) of nuclear size, shape, DNA content, and chromatin organization that predicted distant metastasis and/or PCa-specific death. An LR model also was generated to predict this outcome using a combination of pathologic variables and the best QNG solution. Cox proportional hazards models were generated, and Kaplan-Meier plots were used to display three risk groups based on pathology, QNG, and a combination of these variables. RESULTS: A multivariate LR model using pathology retained lymph node (LN) status, seminal vesicle status, and prostatectomy Gleason score, yielding an area under the curve-receiver operator characteristic (AUC-ROC) of 75% with an accuracy of 59% at 90% sensitivity. The best QNG solution used the variance of 25 NMDs, yielding an AUC-ROC of 84% and an accuracy of 70% at 90% sensitivity. The combined pathology-QNG model retained LN status, prostatectomy Gleason score, and QNG, yielding an AUC-ROC of 86% with an accuracy of 76% at 90% sensitivity. The Cox proportional hazards models produced the following significant univariate and multivariate hazard ratios: QNG, 3.5 and 2.9, respectively; LN, 2.7 and 1.8, respectively; and prostatectomy Gleason score, 2.8 and 2.1, respectively. CONCLUSIONS: Alterations in the structure of tumor nuclei measured by computer-assisted image analysis were strong predictors of PCa progression and death in men with long-term follow-up who had biochemical recurrence after undergoing radical prostatectomy. QNG solutions can serve as a new supplemental biomarker for accurate prediction of PCa progression at the time of surgery.

Adenocarcinoma↗
PubMed2003

Quantitative GSTP1 methylation and the detection of prostate adenocarcinoma in sextant biopsies.

Hypermethylation of the 5' promoter region of the glutathione S-transferase pi gene (GSTP1) occurs at a very high frequency in prostate adenocarcinoma. We compared the results of blinded histologic review of sextant biopsy samples from 72 excised prostates with those obtained using a quantitative methylation-specific polymerase chain reaction assay (QMSP) for GSTP1. Formal surgical pathologic review of the resected prostates was used to determine the number of patients with (n = 61) and without (n = 11) prostate cancer. Histology alone detected prostate carcinoma with 64% sensitivity (95% confidence interval [CI] = 51% to 76%) and 100% specificity (95% CI = 72% to 100%), whereas the combination of histology and GSTP1 QMSP at an assay threshold greater than 10 detected prostate carcinoma with 75% sensitivity (95% CI = 63% to 86%) and 100% specificity (95% CI = 72% to 100%), an 11% improvement (95% CI = 5% to 22%) in sensitivity over histology alone. The combination of histology and GSTP1 QMSP at an assay threshold greater than 5 detected prostate adenocarcinoma with 79% sensitivity (95% CI = 68% to 89%), a 15% improvement (95% CI = 7% to 26%) over histology alone. Thus, GSTP1 QMSP improved the sensitivity of histologic review of random needle biopsies for prostate cancer diagnosis. Further studies should determine whether detection of GSTP1 hypermethylation in a biopsy sample with normal histology indicates the need for an early repeat biopsy at the same site.

Adenocarcinoma↗
PubMed2003

Cytogenetic study of malignant triton tumor: a case report.

Malignant triton tumor (MTT) is a highly malignant neoplasm, classified as a variant of malignant peripheral nerve sheath tumor (MPNST) with rhabdomyoblastic differentiation. Few cytogenetic studies of MTT have been reported using conventional cytogenetic analysis. Here, we report a comprehensive cytogenetic study of a case of MTT using G-banding, Spectral Karyotyping(), and fluorescence in situ hybridization (FISH) for specific regions. A complex hyperdiploid karyotype with multiple unbalanced translocations was observed: 48 approximately 55,XY,der(7)add(7)(p?)dup(7)[2],der(7) t(7;20)(p22;?)ins(20;19)[5],der(7)ins(8;7)(?;p22q36)t(3;8)t(8;20)[15],-8[5],-8[19],r(8)dup(8), +der(8)r(8;22)[4],-9[9],der(11)t(11;20)(p15;?)ins(20;19)[22],der(12)t(8;12)(q21;p13)[21],der(13) t(3;13)(q25;p11),-17,-19,der(19)t(17;19)(q11.2;q13.1),-20,-22,+4 approximately 7r[cp24]/46,XY[13]. The 1995 International System for Human Cytogenetic Nomenclature was followed where possible. Note that breakpoints were frequently omitted where only SKY information was known for a small part of an involved chromosome. Our analysis revealed some breakpoints in common with those previously reported in MTT, MPNST, and rhabdomyosarcoma, namely 7p22, 7q36, 11p15, 12p13, 13p11.2, 17q11.2, and 19q13.1. FISH showed high increase of copy number for MYC and loss of a single copy for TP53.

Aged↗
PubMed2003

Pathological and molecular aspects of prostate cancer.

This review focuses on new findings and controversial issues in the the pathology and molecular biology of adenocarcinoma of the prostate. Since management of high-grade prostatic intraepithelial neoplasia on needle biopsy--the most common precursor lesion to prostate cancer--is the crucial issue with this lesion, we discuss the risk of cancer subsequent to this histological diagnosis and the issue of whether such neoplasia should be regarded as carcinoma-in-situ. We also look at prostate cancer itself, starting with its diagnosis, reporting on needle biopsy, and reviewing how the most frequently used grading system, the Gleason grading system, affects treatment. The molecular basis of prostate cancer includes inheritable and somatic genetic changes (tumour suppressor genes, loss of heterozygosity, gene targets and regions of chromosomal gain, CpG island promoter methylation, invasion and metastasis suppressor genes, telomere shortening, and genetic instability). Changed gene expression (eg, proliferation-related genes, changes in the androgen receptor, apoptosis and stress-response genes) have potential as biomarkers and therapeutic targets in prostate cancer.

Adenocarcinoma↗
PubMed2003

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.

Adenocarcinoma↗
PubMed2003

Quantitative biopsy pathology for the prediction of pathologically organ-confined prostate carcinoma: a multiinstitutional validation study.

BACKGROUND: Quantitative biopsy pathology with prostate specific antigen significantly improves the prediction of pathologic stage in patients with clinically localized prostate carcinoma (PCa). The authors recently reported a computational model for predicting patient specific likelihood of organ confinement of PCa using biopsy pathology and clinical data. The current study validates the initial models and presents an new, improved tool for clinical decision making. METHODS: The authors assessed 10 biopsy pathologic parameters and 2 clinical parameters using data from two institutions. Of 1287 patients, 798 men had pathologically organ confined (OC) PCa, 282 men had nonorgan-confined disease with capsular penetration (NOC-CP) only, and 207 men showed seminal vesicle or lymph node invasion (NOC-AD) after undergoing pelvic lymphadenectomy and radical prostatectomy. Patient input data were evaluated by ordinal logistic (OLOGIT) and neural network (NN) models; and the likelihood of developing OC, NOC-CP, or NOC-AD disease was calculated for the combined and separate data sets and was compared with the results from original presentation. In addition, a new two-output model was constructed (OC/NOC-CP vs. NOC-AD). RESULTS: The three-output OLOGIT and NN models predicted OC disease with 95.0% and 98.6% accuracy, respectively, for the combined data set and with 93.0% and 98.6% accuracy, respectively, on subset analysis. The combined accuracy for predicting OC, NOC-CP, and NOC-AD disease in the entire validation set was 66.7% for OLOGIT model and 66.0% for the NN model. The two-output OLOGIT and NN models correctly predicted 94.9% and 100.0% of all OC/NOC-CP disease, respectively. CONCLUSIONS: Both computation models predicted OC PCa with an accuracy of 93.0-98.6% when they were validated with two different data sets. The OLOGIT and NN-based, two-output model permitted an appropriate treatment decision for 85.2-90.2% of patients. These data support the use of quantitative pathology and clinical data-based decision modeling to manage patients with clinically localized PCa.

Biopsy↗
PubMed2003

Hypermethylation of the human glutathione S-transferase-pi gene (GSTP1) CpG island is present in a subset of proliferative inflammatory atrophy lesions but not in normal or hyperplastic epithelium of the prostate: a detailed study using laser-capture microdissection.

Somatic inactivation of the glutathione S-transferase-pi gene (GSTP1) via CpG island hypermethylation occurs early during prostate carcinogenesis, present in approximately 70% of high-grade prostatic intraepithelial neoplasia (high-grade PIN) lesions and more than 90% of adenocarcinomas. Recently, there has been a resurgence of the concept that foci of prostatic atrophy (referred to as proliferative inflammatory atrophy or PIA) may be precursor lesions for the development of prostate cancer and/or high-grade PIN. Many of the cells within PIA lesions contain elevated levels of GSTP1, glutathione S-transferase-alpha (GSTA1), and cyclooxygenase-II proteins, suggesting a stress response. Because not all PIA cells are positive for GSTP1 protein, we hypothesized that some of the cells within these regions acquire GSTP1 CpG island hypermethylation, increasing the chance of progression to high-grade PIN and/or adenocarcinoma. Separate regions (n =199) from 27 formalin-fixed paraffin-embedded prostates were microdissected by laser-capture microdissection (Arcturus PixCell II). These regions included normal epithelium (n = 48), hyperplasticepithelium from benign prostatic hyperplasia nodules (n = 22), PIA (n = 64), high-grade PIN (n = 32), and adenocarcinoma (n = 33). Genomic DNA was isolated and assessed for GSTP1 CpG island hypermethylation by methylation-specific polymerase chain reaction. GSTP1 CpG island hypermethylation was not detected in normal epithelium (0 of 48) or in hyperplastic epithelium (0 of 22), but was found in 4 of 64 (6.3%) PIA lesions. The difference in the frequency of GSTP1 CpG island hypermethylation between normal or hyperplastic epithelium and PIA was statistically significant (P = 0.049). Similar to studies using nonmicrodissected cases, hypermethylation was found in 22 of 32 (68.8%) high-grade PIN lesions and in 30 of 33 (90.9%) adenocarcinoma lesions. Unlike normal or hyperplastic epithelium, GSTP1 CpG island hypermethylation can be detected in some PIA lesions. These data support the hypothesis that atrophic epithelium in a subset of PIA lesions may lead to high-grade PIN and/or adenocarcinoma. Because these atrophic lesions are so prevalent and extensive, even though only a small subset contains this somatic DNA alteration, the clinical impact may be substantial.

Atrophy↗
PubMed2003

Accuracy of gleason grading by practicing pathologists and the impact of education on improving agreement.

The aims of this study were to evaluate the accuracy of Gleason grading for prostatic adenocarcinoma among practicing pathologists in Japan and to determine the influence of education on this accuracy. Using a case-oriented approach, 16 hematoxylin and eosin-;stained glass slides with consensus scores established by 4 urologic pathologists were reviewed by 91 pathologists, divided into 2 groups. In group A, average agreements with consensus scores before and after an educational lecture were 55.7% (n = 17) and 68.4% (n = 25), and average kappa values were 0.43 and 0.67, respectively. Twelve pathologists reviewed slides twice in a different order, with average agreements of 59.5% and 77.6%, and average kappa values of 0.48 and 0.69 before and after the lecture, yielding a statistically significant improvement. In group B, the average agreement before providing an atlas with a tutorial was 61.3% (n = 61), and the kappa value was 0.44. In the second round, the average agreement was 74.5% (n = 39), and the kappa value was 0.68. Among 39 pathologists who reviewed slides twice, the average agreement in the first round was 58.8%, and the kappa value was 0.42. Improvement of both the average agreement and the kappa value were statistically significant. The average improvement in kappa values among participants who reviewed slides twice was 0.22 in group A and 0.27 in group B, a difference that is not statistically significant. Combining both groups, the incidence of concordant scores for 16 cases rose from 58.9% to 75.4%, an average increase of 16.5%. The undergrading of score 5-7 lesions was significantly reduced, from 36.3% to 14.2%. With respect to demographic factors, pathologists signing out more than 5000 cases per year showed a better agreement than those with more than 1000 cases per year (48.9% versus 78.8%; P = 0.031). These results indicate that the general agreement of Gleason scores among practicing pathologists in Japan was comparable with those in the Western countries as reported in the literature. Although this requires further improvement, both the lecture and the printed material had a similar influence on the degree of improvement.

Adenocarcinoma↗
PubMed2003

Should each core with prostate cancer be assigned a separate gleason score?

If multiple biopsy cores contain prostate cancer with differing Gleason scores, should an overall Gleason score be assigned, or should each core be graded separately? We obtained data on 127 men with prostate cancer on needle biopsy who underwent subsequent radical prostatectomy at our institution. We compared the Gleason scores found on needle biopsy with the grade and stage (organ-confined, extra-prostatic extension, positive seminal vesicles or lymph nodes) at radical prostatectomy. On biopsy, 40 men had a pure Gleason score of 4 + 3 = 7, 25 men had a Gleason score of 4 + 3 = 7 with a Gleason score of 3 + 3 = 6 on a separate core of the biopsy specimen, 27 men had a pure Gleason score of 4 + 4 = 8, and 35 men had a Gleason score of 4 + 4 = 8 with separate cores containing Gleason pattern grade 3. A Gleason score of 4 + 4 = 8 with pattern grade 3 in other cores had a more advanced stage than a pure Gleason score of 4 + 3 = 7 (P = 0.008). There was no clear pattern analyzing pathological stage of men with a pure Gleason score of 4 + 3 = 7 in comparison with those with Gleason scores of 4 + 3 = 7 and 3 + 3 = 6 in other cores. The group with a Gleason score of 4 + 4 = 8 and Gleason pattern grade 3 on other cores had a higher overall grade on radical prostatectomy than the group with a pure Gleason score of 4 + 3 = 7 (P = 0.001). If one had assigned an overall Gleason score, then a biopsy with Gleason score 4 + 4 = 8 on 1 or more cores and some pattern grade 3 in other cores, would be designated as a Gleason score of 4 + 3 = 7. Based on our findings, patients with a Gleason score of 4 + 4 = 8 on one or more cores with pattern grade 3 in other cores should be given a final Gleason score of 4 + 4 = 8 instead of 4 + 3 = 7, because these patients are more likely to have higher stage and grade on radical prostatectomy, comparable to a pure Gleason score of 4 + 4 = 8. Each core should be assigned a separate Gleason score, especially in cases with high Gleason score cancer on at least 1 core.

Adenocarcinoma↗
PubMed2003

Threshold for diagnosing prostate cancer over time.

Paralleling the detection of earlier prostate cancer over the last several years, there have been numerous efforts to educate practicing pathologists on the diagnosis of limited prostate cancer on needle biopsy via journal articles, Web sites, books, and educational courses. The current study was undertaken to assess whether the threshold for the diagnosis of prostate cancer on needle biopsy has lowered over time. One thousand twelve prostate needle biopsy cases obtained in consultation by 1 of the authors because of diagnostic concerns over a period of 12 weeks (November 15, 2001 to February 15, 2002) were reviewed. Cases referred by either the patient or clinicians were excluded. The final diagnoses in this series were compared with a previously published series of needle biopsy cases of the prostate seen in consultation by the same author in 1993-1994. The percentage of cancer in the 2001-2002 series was 55.1%, compared with 69.6% for the 1993-1994 series. The mean and median numbers of malignant glands in the 2001-2002 series (mean, 21.9; median, 14; range, 2 to 296) were significantly smaller than in the 1993-1994 series (mean, 31.0; median, 20; range, 2 to 300; P<0.00001). The incidence of atypical glands that were suspicious for but not diagnostic of carcinoma was 23.9% in the 2001-2002 series and was 10.7% in the 1993-1994 series. The mean and median numbers of atypical glands in the 2001-2002 series were 9.4 and 6, respectively (range, 1 to 70); these parameters were not available for the previous series. The percentage of high-grade prostatic intraepithelial neoplasia diagnoses was similar in the 2001-2002 and 1993-1994 series (5.1% and 4.6%, respectively), as was the overall frequency of benign cases (15.8% and 15.1%, respectively). The percentage of cases that were accompanied by immunohistochemical stains for 34betaE12 in the 2001-2002 series was 44.4%, which was much more than the 2.5% seen in the 1993-1994 series; if anything, this should have resulted in a lower atypical rate in the current series. In more recent years, cases sent for consultation have more limited cancer, with a correspondingly higher percentage of cases that are diagnosed as atypical, yet not diagnostic of cancer. The number of atypical glands in the recent series was very limited, such that a change over time in the threshold for diagnosing cancer by the consultant is an unlikely explanation. It appears that pathologists are becoming more skilled at diagnosing limited prostate cancer and are referring predominantly cases with fewer cancer glands and more difficult atypical cases with few glands.

Adenocarcinoma↗
PubMed2003

Multilocular prostatic cystadenoma with high-grade prostatic intraepithelial neoplasia.

Multilocular prostatic cystadenoma is a rarely encountered neoplasm located in the midline between the bladder and rectum that is either attached to the prostate by a pedicle or separate from the prostate entirely. Histologically and immunohistochemically these lesions resemble benign prostate tissue. We report the first case of this entity for which multifocal high-grade prostatic intraepithelial neoplasia (PIN) is identified. Conceptually, the finding of high-grade PIN in multilocular prostatic cystadenomas provides further evidence that these lesions are fully analogous to the prostate gland not only in their morphology and immunohistochemistry but also in their predilection for the same diseases.

Cystadenoma↗
PubMed2003

Immunohistochemical staining of prostate cancer with monoclonal antibodies to the precursor of prostate-specific antigen.

OBJECTIVES: To characterize the immunohistochemical staining (IHS) of precursor forms of prostate-specific antigen (pro-PSA) forms in prostate cancer, high-grade prostatic intraepithelial neoplasia (HGPIN), and benign tissue from the peripheral and transition zones. Pro-PSA have previously been shown to be more concentrated in prostate cancer tissue extracts than in benign tissue. METHODS: Prostate needle biopsies showing HGPIN (22 sections, 11 patients) and adenocarcinoma (30 sections, 21 patients) and 17 radical prostatectomy and 3 open prostatectomy specimens were identified from the surgical pathology files of Johns Hopkins Hospital. IHS was performed on formalin-fixed, paraffin-embedded sections using one monoclonal antibody (mAB) against pro-PSA with a truncated pro-leader peptide containing two amino acids, [-2]pPSA, and a second mAB against native pro-PSA ([-5/-7]pPSA). RESULTS: The mABs were specific for both benign and malignant prostatic glandular tissue and did not stain stromal, vascular, or colonic tissue when present in the specimens. All sections with HGPIN and/or adenocarcinoma showed staining with both mABs. HGPIN was strongly positive in most cases (66.1%). The native pro-PSA mAB showed little differential between cancer and benign glands, and the mAB to the truncated [-2]pPSA stained cancer tissue more strongly than benign tissue. Benign atrophic glands often showed negative or weak/patchy staining. No difference was found in the staining pattern between benign glands in the peripheral zone and transition zone. CONCLUSIONS: This study is the first to demonstrate that mABs to pro-PSA can be used as specific IHS for benign and malignant prostatic tissue. [-2]pPSA appears to be preferentially more concentrated in cancer tissue than in benign glands, correlating with previous tissue extract studies. Unlike previous studies with PSA staining, the IHS for pro-PSA remained uniform among the different tumor grades. Therefore, pro-PSA may be a useful marker in differentiating high-grade prostate adenocarcinoma from other non-prostate carcinomas.

Adenocarcinoma↗