Cases Of High-grade Prostatic Intraepithelial Neoplasia Research Articles

<p>ERG expression in prostate cancer biopsies with and without high-grade prostatic intraepithelial neoplasia: a study in Jordanian Arab patients</p>

Background: High-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precancerous lesion for prostatic adenocarcinoma (PCa). Recent molecular studies have shown that HGPIN can harbor TMPRSS2-ERG fusion, a genetic marker also associated with PCa, which may provide an additional risk stratification tool for HGPIN, especially when present as an isolated lesion. Our aim was to assess the frequency of HGPIN and ERG expression in a cohort of prostatic needle core biopsies from Jordanian-Arab patients with PCa.Materials and methods: We studied 109 needle core biopsies from patients with PCa. Clinical data, including age and preoperative prostate specific antigen (PSA) level, were obtained from patients’ medical records.Results: HGPIN was present in 31 (28.4 %) of the 109 cases. Of the HGPIN cases, 13 (41.9%) expressed ERG immunostain. ERG expression in HGPIN was independent of patient age at presentation (P=0.4), pre-operative PSA (P=0.9), and the grade, using the novel Grade Groups (P=0.5).Conclusion: The frequency of HGPIN in our cohort appears similar to the one found in the Western patient populations and demonstrates a comparable frequency of ERG expression in these lesions.

Prostatic adenocarcinoma and prostatic intraepithelial neoplasia: A tale of the autopsy model in a Nigerian tertiary hospital

Introduction: The frequency of clinical prostatic adenocarcinoma and high-grade prostatic intraepithelial neoplasia (HGPIN) in a certain population could be similar to the prevalent model of latent adenocarcinoma as well as to the frequency and extent of HGPIN. The aim of this prospective postmortem study is to determine the prevalence of occult adenocarcinoma and HGPIN and contrasting same with the existing clinical model in the same environment. Subjects and Methods: Adult individuals who died from ailments unrelated to diseases of the prostate glands were the target population using a calculated minimum sample size of 72 cases. The partial sampling method was employed. Sections were assessed for prostatic adenocarcinoma and HGPIN. The biodata and clinical diagnosis were obtained from stored records. Results: Seven patients had occult adenocarcinoma representing 8.1% of the study population of 86 cases. Their median age was 60 years. It had a peak incidence in the sixth decade, with a prevalence of 42.85% in the subset of the study population who had the disease. Gleason's grade 3 and score 6 were the most frequent grades and scores encountered in this study. Those with occult adenocarcinoma were graded International Society of Urological Pathologist (ISUP) 1 using the ISUP grade group system. There were five cases of HGPIN in this study. Their median age was 54 years. It had a peaked incidence in the eighth decade. Conclusion: There exists a subset of the population with occult prostatic adenocarcinoma and HGPIN. These subclinical prostatic lesions may become clinically apparent if these patients had lived long enough, and hence, the prostate should be considered as a possible primary site of metastatic carcinoma because of this concept “occult adenocarcinoma.”

Urinary biomarkers for the detection of prostate cancer in patients with high‐grade prostatic intraepithelial neoplasia

High-grade prostatic intraepithelial neoplasia (HGPIN) is a recognized precursor stage of PCa. Men who present HGPIN in a first prostate biopsy face years of active surveillance including repeat biopsies. This study aimed to identify non-invasive prognostic biomarkers that differentiate early on between indolent HGPIN cases and those that will transform into actual PCa. We measured the expression of 21 candidate mRNA biomarkers using quantitative PCR in urine sediment samples from a cohort of 90 patients with initial diagnosis of HGPIN and a posterior follow up of at least two years. Uni- and multivariate statistical analyses were applied to analyze the candidate biomarkers and multiplex models using combinations of these biomarkers. PSMA, PCA3, PSGR, GOLM, KLK3, CDH1, and SPINK1 behaved as predictors for PCa presence in repeat biopsies. Multiplex models outperformed (AUC = 0.81-0.86) the predictive power of single genes, including the FDA-approved PCA3 (AUC = 0.70). With a fixed sensitivity of 95%, the specificity of our multiplex models was of 41-58%, compared to the 30% of PCA3. The PPV of our models (30-38%) was also higher than the PPV of PCA3 (27%), suggesting that benign cases could be more accurately identified. Applying statistical models, we estimated that 33% to 47% of repeat biopsies could be prevented with a multiplex PCR model, representing an easy applicable and significant advantage over the current gold standard in urine sediment. Using multiplex RTqPCR-based models in urine sediment it is possible to improve the current diagnostic method of choice (PCA3) to differentiate between benign HGPIN and PCa cases.

MP6-01 URINARY BIOMARKERS FOR THE DETECTION OF PROSTATE CANCER IN PATIENTS WITH HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA (HGPIN).

You have accessJournal of UrologyProstate Cancer: Markers II1 Apr 2015MP6-01 URINARY BIOMARKERS FOR THE DETECTION OF PROSTATE CANCER IN PATIENTS WITH HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA (HGPIN). Juan M. Bastarós, Tamara Sequeiros, José Placer, Jacques Planas, Lucas Regis, Milagros Sánchez, Marina Rigau, Melania Montes, Inés de Torres, Jaume Reventós, Andreas Doll, and Juan Morote Juan M. BastarósJuan M. Bastarós More articles by this author , Tamara SequeirosTamara Sequeiros More articles by this author , José PlacerJosé Placer More articles by this author , Jacques PlanasJacques Planas More articles by this author , Lucas RegisLucas Regis More articles by this author , Milagros SánchezMilagros Sánchez More articles by this author , Marina RigauMarina Rigau More articles by this author , Melania MontesMelania Montes More articles by this author , Inés de TorresInés de Torres More articles by this author , Jaume ReventósJaume Reventós More articles by this author , Andreas DollAndreas Doll More articles by this author , and Juan MoroteJuan Morote More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.248AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Men with suspicion of prostate cancer (PCa) are referred for prostatic biopsy (PB), and some of them will present HGPIN (a commonly accepted precursor of PCa) in this first PB. Those patients frequently face several years of active surveillance including repeat PBs. Previously, our research group showed that PCA3 and PSGR gene expression in urine sediment could be useful biomarkers for the detection of PCa in benign prostatic hyperplasia cases. Although with a lower efficacy, we also observed that PCA3 was able to detect PCa in those patients with a previous diagnosis of HGPIN. The aim of this study is to identify urinary biomarkers that could differentiate between indolent HGPIN cases and those who actually present PCa. METHODS From a cohort of 114 patients with diagnosis of HGPIN (in a first PB recommended due to increased serum PSA levels (>4ng/mL) and/or an abnormal diagnostic DRE), urine sediment samples were obtained, after DRE within days before a repeat biopsy after a posterior follow up of at least two years. Reverse-transcriptase PCR (RTqPCR) of extracted RNA was conducted to determine expression of 6 endogenous genes and 17 target genes, all of them putative PCa biomarkers. Univariate tests and univariate and multivariate logistic regressions were used to examine associations between PCa diagnostic status and testing genes. All possible models were created using combinations of the most significant genes obtained in the univariate analysis and multivariate logistic regression was applied to them. The number of PBs potentially avoided by the use of the proposed biomarkers was calculated. RESULTS By univariate statistical analysis of the obtained data, it was found that PSMA, PCA3, PSGR, GOLM, KLK3 and CDH1 were significant predictors of PCa in repeat PB. Multiplex models that use the PCa biomarkers KLK3, PSMA, PSGR, GOLM1 and CDH1 (AUC=0.81-0.86) outperform all the assayed genes, including PCA3 (AUC=0.70), when used individually. With a fixed sensitivity of 95%, the specificity of the models was of 41–58%, compared to the 30% of PCA3. Applying these models, it would be possible to save from 33% and up to 47% of the repeat biopsies practiced. CONCLUSIONS A multiplexed RTqPCR assay on urine sediments from patients presenting for a repeat PB due to a diagnosis of HGPIN can significantly improve the predictive ability when compared to PCA3 or any other assayed gene when used alone. Further evaluation and validation of these biomarkers in larger and independent cohorts is highly desirable, in order to confirm these results. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e54 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Juan M. Bastarós More articles by this author Tamara Sequeiros More articles by this author José Placer More articles by this author Jacques Planas More articles by this author Lucas Regis More articles by this author Milagros Sánchez More articles by this author Marina Rigau More articles by this author Melania Montes More articles by this author Inés de Torres More articles by this author Jaume Reventós More articles by this author Andreas Doll More articles by this author Juan Morote More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

ERG Rearrangement for Predicting Subsequent Cancer Diagnosis in High-Grade Prostatic Intraepithelial Neoplasia and Lymph Node Metastasis

We aimed to analyze whether ERG rearrangement in biopsies could be used to assess subsequent cancer diagnosis in high-grade prostatic intraepithelial neoplasia (HGPIN) and the risk of lymph node metastasis in early prostate cancer. Samples from 523 patients (361 with early prostate cancer and 162 with HGPIN) were collected prospectively. On the basis of the cutoff value established previously, the 162 patients with HGPIN were stratified to two groups: one with an ERG rearrangements rate ≥1.6% (n = 59) and the other with an ERG rearrangements rate <1.6% (n = 103). For the 361 prostate cancer cases undergoing radical prostatectomy, 143 had pelvic lymph node dissection (node-positive, n = 56 and node-negative, n = 87). All ERG rearrangement FISH data were validated with ERG immunohistochemistry. A total of 56 (of 59, 94.9%) HGPIN cases with an ERG rearrangements rate ≥1.6% and 5 (of 103, 4.9%) HGPIN cases with an ERG rearrangements rate <1.6% were diagnosed with prostate cancer during repeat biopsy follow-ups (P < 0.001). There were significant differences in ERG rearrangement rates between lymph node-positive and -negative prostate cancer (P < 0.001). The optimal cutoff value to predict lymph node metastasis by ERG rearrangement was established, being 2.6% with a sensitivity at 80.4% [95% confidence interval (CI), 67.6-89.8] and a specificity at 85.1% (95% CI, 75.8-91.8). ERG protein expression by immunohistochemistry was highly concordant with ERG rearrangement by FISH. The presence of ERG rearrangement in HGPIN lesions detected on initial biopsy warrants repeat biopsies and measuring ERG rearrangement could be used for assessing the risk of lymph node metastasis in early prostate cancer.

Immunohistochemical Staining of Slit2 in Primary and Metastatic Prostatic Adenocarcinoma

BACKGROUND: Conflicting roles for Slit2, a protein involved in mediating the processes of cell migration and chemotactic response, have been previously described in prostate cancer. Here we use immunohistochemistry to evaluate the expression of Slit2 in normal donor prostate (NDP), benign prostatic hyperplasia (BPH), high-grade prostatic intraepithelial neoplasia (HGPIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma (PCa), and metastatic prostatic adenocarcinoma (Mets). METHODS: Tissue microarrays were immunostained for Slit2. The staining intensities were quantified using automated image analysis software. The data was statistically analyzed using one-way analysis of variance with subsequent Tukey tests for multiple comparisons or a nonparametric equivalent. Eleven cases of NDP, 35 cases of NAC, 15 cases of BPH, 35 cases of HGPIN, 106 cases of PCa, and 37 cases of Mets were analyzed. RESULTS: Specimens of PCa and HGPIN had the highest absolute staining for Slit2. Significant differences were seen between PCa and NDP (P < .05), PCa and NAC (P < .05), HGPIN and NDP (P < .05), and HGPIN and NAC (P < .05). Whereas the average Mets staining was not significantly different from NDP or NAC, several individual Mets cases featured intense staining. CONCLUSIONS: To our knowledge, this represents the first study comparing the immunohistochemical profiles of Slit2 in PCa and Mets to specimens of HGPIN, BPH, NDP, and NAC. These findings suggest that Slit2 expression can be increased in HGPIN, PCa, and Mets, making it a potentially important biomarker for prostate cancer.

Immunohistochemical analysis of ezrin-radixin-moesin-binding phosphoprotein 50 in prostatic adenocarcinoma

BackgroundEzrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is an adapter protein which has been shown to play an active role in a wide variety of cellular processes, including interactions with proteins related to both tumor suppression and oncogenesis. Here we use immunohistochemistry to evaluate EBP50's expression in normal donor prostate (NDP), benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma (PCa), and metastatic prostatic adenocarcinoma (Mets).MethodsTissue microarrays were immunohistochemically stained for EBP50, with the staining intensities quantified using automated image analysis software. The data were statistically analyzed using one-way ANOVA with subsequent Tukey tests for multiple comparisons. Eleven cases of NDP, 37 cases of NAC, 15 cases of BPH, 35 cases of HGPIN, 103 cases of PCa, and 36 cases of Mets were analyzed in the microarrays.ResultsSpecimens of PCa and Mets had the lowest absolute staining for EBP50. Mets staining was significantly lower than NDP (p = 0.027), BPH (p = 0.012), NAC (p < 0.001), HGPIN (p < 0.001), and PCa (p = 0.006). Additionally, HGPIN staining was significantly higher than NAC (p < 0.009) and PCa (p < 0.001).ConclusionsTo our knowledge, this represents the first study comparing the immunohistochemical profiles of EBP50 in PCa and Mets to specimens of HGPIN, BPH, NDP, and NAC and suggests that EBP50 expression is decreased in Mets. Given that PCa also had significantly higher expression than Mets, future studies are warranted to assess EBP50's potential as a prognostic biomarker for prostate cancer.

Can molecular markers stratify the diagnostic value of high-grade prostatic intraepithelial neoplasia?

The diagnostic performance of isolated high-grade prostatic intraepithelial neoplasia in prostatic biopsies has recently been questioned, and molecular analysis of high-grade prostatic intraepithelial neoplasia has been proposed for improved prediction of prostate cancer. Here, we retrospectively studied the value of isolated high-grade prostatic intraepithelial neoplasia and the immunohistochemical markers α-methylacyl coenzyme A racemase, Bcl-2, annexin II, and Ki-67 for better risk stratification of high-grade prostatic intraepithelial neoplasia in our local Swiss population. From an initial 165 diagnoses of isolated high-grade prostatic intraepithelial neoplasia, we refuted 61 (37%) after consensus expert review. We used 30 reviewed high-grade prostatic intraepithelial neoplasia cases with simultaneous biopsy prostate cancer as positive controls. Rebiopsies were performed in 66 patients with isolated high-grade prostatic intraepithelial neoplasia, and the median time interval between initial and repeat biopsy was 3 months. Twenty (30%) of the rebiopsies were positive for prostate cancer, and 10 (15%) showed persistent isolated high-grade prostatic intraepithelial neoplasia. Another 2 (3%) of the 66 patients were diagnosed with prostate cancer in a second rebiopsy. Mean prostate-specific antigen serum levels did not significantly differ between the 22 patients with prostate cancer and the 44 without prostate cancer in rebiopsies, and the 30 positive control patients, respectively (median values, 8.1, 7.7, and 8.8 ng/mL). None of the immunohistochemical markers, including α-methylacyl coenzyme A racemase, Bcl-2, annexin II, and Ki-67, revealed a statistically significant association with the risk of prostate cancer in repeat biopsies. Taken together, the 33% risk of being diagnosed with prostate cancer after a diagnosis of high-grade prostatic intraepithelial neoplasia justifies rebiopsy, at least in our not systematically prostate-specific antigen-screened population. There is not enough evidence that immunohistochemical markers can reproducibly stratify the risk of prostate cancer after a diagnosis of isolated high-grade prostatic intraepithelial neoplasia.

Eradication of prostatic high grade intraepithelial neoplasia: Hypothesis and clinical proof

1534 Background: Recently normal prostate tissue has been found to contain a high concentration of retinoid X receptors (RXRs), they are found in the highest concentrations in ectodermal tissue. Loss of these receptors is associated with prostatic intraepithelial neoplasia (PIN), and can be present in patients with a normal PSA. There are 115,000 cases of high grade PIN discovered yearly in the United States.The drug bexarotene used to treat cutaneous T cell lymphoma (CTCL). The compound is not a true retinoid in structure, perusal of the structure reveals two aromatic rings one of which contains a carboxy group which would make one anticipate strong hydrogen bonding when it undergoes binding to the RXRs as if it were a retinoid, resulting in “up regulation” of the tissue with increase in differentiation to normal tissue. Based upon this it was felt that it would be fruitful to try bexarotene in High Grade PIN. Method: The diagnosis was based upon 12 biopsies which were done in conjunction with ultrasound localization of the biopsy site, with careful recording of there anatomical position. The patient was started on bexarotene 225 mg per day. The drug was given as a single dose once daily; this dose is 40% of the dose normally used to treat CTCL. The drug was administered for 30 doses During the period of therapy the patient was on Atorvastin T4 total was within the normal range. Results: Four weeks following the last dose of bexarotene the prostate was rebiopsied with 12 biopsies taken. Six of the biopsies were taken from the putative area, the rest in an enlarging target like pattern. The repeat biopsy was negative for the presence of PIN. 14 months later 12 more biopsies were obtained using the same technique, these repeat biopsies were also found to be negative; ie. 24 negative biopsies over 14 months. It is unlikely that the previously involved area was missed. Conclusion: If a mechanism of action were to be formulated, the induction of and increase in RXRs in normal prostate cells would be reasonable. Cells that undergo the formation of PIN, strong hydrogen bonding and inability of those cells to produce more receptors could result in apoptosis. Undoubtedly further study is required to evaluate the effect of this drug in high grade PIN. No significant financial relationships to disclose.

The utility of Ki-67 expression in the differential diagnosis of prostatic intraepithelial neoplasia and ductal adenocarcinoma

Cribriform and/or papillary prostatic lesions observed on limited tissue, such as needle biopsy, can pose diagnostic dilemmas. One such area of difficulty is the distinction between papillary and/or cribriform prostatic high-grade prostatic intraepithelial neoplasia (HG-PIN) and ductal adenocarcinoma. Over 48 months, we identified 17 cases of ductal adenocarcinoma and 17 cases of HG-PIN from radical retropubic prostatectomy specimens. The HG-PIN lesions were in all cases associated with an acinar prostatic adenocarcinoma component. For each case, we evaluated the proliferative activity, assessed by Ki-67 immunohistochemistry. The majority (82%) of ductal adenocarcinomas were composed of mixed papillary and cribriform patterns, with the remaining demonstrating pure papillary or cribriform patterns. The HG-PIN lesions showed a papillary, cribriform, or mixed papillary/cribriform architecture. The proliferative activity, defined as Ki-67 labeling index, was statistically higher in ductal adenocarcinoma (mean 33%, range 21%-66%) as compared with HG-PIN (mean 6%, range 2%-15%), with no overlap in the Ki-67 indices (P = 0001). A combination of histological features and measurements of cellular proliferation may be helpful to distinguish HG-PIN from ductal adenocarcinoma in limited prostatic tissue samples.

Neoplasia intraepitelial prostática aislada y positividad para adenocarcinoma en la rebiopsia. Revisión de nuestra serie

ObjetiveTo review the incidence of isolated prostatic intraepithelial neoplasia (PIN) as well as the positive prostate cancer results in repeat biopsy in our series of transrectal biopsy of the prostate. We compare these results with the actual literature Materials and methodsWe review the 2.475 transrectal ultrasound guided biopsies of the prostate made in our department from January 1992 to June 2004 looking for intraepithelial neoplasia and looking in particular for isolated High-grade PIN ( HGPIN). We review repeat biopsies made at this patients and the likelihood of detecting prostate cancer in them. ResultsThe diagnosis of PIN was found in 31 biopsies, 13 of them were isolated HGPIN what means a 0,52% incidence of the total biopsies performed in our department. We performed 7 repeat biopsies of the 13 cases in a period from 3 months to 2 years after the first biopsy, and we found 3 cases of prostate cancer what means that 43% of isolated HGPIN with repeated biopsy showed prostate cancer. The mean age of the patients studied was 67 years (range 53-88). The median PSA value of the studied cases was 9,8 ng /ml. The Gleason score of the positive biopsies was always between 3 and 7. In our series, age and PSA levels did not have correlation with the positive results for prostate cancer in repeated biopsies. ConclusionIn spite of a lower number of HGPIN cases in our series, the positive for prostate cancer in repeated biopsy ( 43%) is similar to the incidence reported in literature so it is advisable rigorous controls and repeated biopsies for these patients

Expression of Bcl-2, Bax, and p53 in high-grade prostatic intraepithelial neoplasia and localized prostate cancer: relationship with apoptosis and proliferation.

Apoptosis-regulating genes have been shown to be important in the biology of prostate cancer. The aim of this study was to examine and correlate the expression of the apoptosis-regulating genes bcl-2, bax, and p53 with the frequency of apoptosis and rate of proliferation in benign prostatic epithelium (BP), prostate cancer, and high-grade prostatic intraepithelial neoplasia (HGPIN), which is currently considered the most likely precursor of prostate cancer. Forty-four patients with histologically proven prostate cancer were investigated. All the men underwent radical prostatectomy. Immunohistochemistry was performed to assess expression of bcl-2, bax, and p53, and proliferation rate, as measured by the Ki-67 index. The frequency of apoptotic bodies was assessed by morphological criteria. The apoptotic index (AI) was highest in prostate cancer, and was significantly greater in HGPIN compared to benign prostate. The Ki-67 index was greatest in cancer, intermediate in HGPIN, and lowest in BP. The AI was increased in areas of BP in patients treated with neoadjuvant androgen ablation. No change in AI was seen in treated cases of HGPIN or cancer. Accumulation of p53 protein was infrequent in prostate cancer (2/43: 4.6%), and was absent in HGPIN. Bcl-2 overexpression was present in 2.3% of cancers (1/43) and in 34.9% of cases of HGPIN (15/43). Bax expression was seen in all cases of cancer and HGPIN. There was no correlation between bcl-2 expression and the apoptotic and Ki-67 indices in HGPIN. p53 and bcl-2 expression is infrequent in clinically organ confined prostate cancer. Bcl-2 expression is significantly higher in HGPIN than in both the associated prostate cancer and BP. The AI and Ki-67 index appeared intermediate in the putative precursor lesion HGPIN compared to prostate cancer and BP.

Unusual histologic types of high-grade prostatic intraepithelial neoplasia.

High-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precursor proliferation of peripheral zone, moderately to poorly differentiated prostatic adenocarcinomas. The usual cell type of the epithelial lining of HGPIN is a glandular epithelial cell with characteristic nuclear abnormalities. Here we report nine cases of unusual types of HGPIN, including three cases of signet-ring cell HGPIN, one case of small cell neuroendocrine HGPIN, and five cases of HGPIN with distinctive mucinous features. The three examples of signet-ring cell PIN were all associated with an invasive primary signet-ring cell carcinoma of the prostate. The HGPIN assumed a classical tufted and micropapillary architectural growth pattern, with the constituent cells exhibiting a morphologic appearance identical to that of the invasive signet-ring cells. The intraepithelial and invasive signet-ring cells were mucin negative and were immunoreactive for prostate-specific antigen (PSA). A fourth case displayed a mixed intraepithelial glandular-small cell neoplastic proliferation, where intraepithelial small cells were histologically identical to surrounding invasive small cell carcinoma cells. The small cell HGPIN and invasive small cell carcinoma cells were positive for the neuroendocrine markers chromogranin, synaptophysin, and neuron-specific enolase. In five cases, mucinous distension of HGPIN glands, producing a flat pattern of the epithelial lining layer, comprised the third unusual pattern of HGPIN. These blue mucinous secretions were readily detected by hematoxylin and eosin staining and were composed of both neutral (periodic acid-Schiff-positive) and acidic (alcian blue-positive) mucins. Herein we document the existence of an intraepithelial proliferation of neoplastic cell types-small cell neuroendocrine and signet-ring cell-that are usually considered as stromal-invasive cells in the prostate. The presence of these rare prostatic cell types in both HGPIN and invasive carcinoma provides further support for a close relationship between HGPIN and invasive carcinoma of the prostate. All three unusual types of HGPIN-signet-ring cell, small cell neuroendocrine, and mucinous-are important to diagnostically recognize because of the strength of association of HGPIN with invasive carcinoma.

Diagnostic distance of high grade prostatic intraepithelial neoplasia from normal prostate and adenocarcinoma.

OBJECTIVE: To develop a distance measure based methodology to support the morphological evaluation of high grade prostatic intraepithelial neoplasia (PIN), a direct precursor of prostate cancer. METHODS: Eight morphological and...