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PubMed1998

Cribriform carcinoma of the prostate and cribriform prostatic intraepithelial neoplasia: incidence and clinical implications.

Cribriform neoplasia of the prostate can be recognized easily. However, controversy persists regarding terminology, particularly with the intraductal spread of cribriform neoplasia; some consider this "intraductal carcinoma," whereas consensus meetings defined these lesions as high-grade cribriform prostatic intraepithelial neoplasia (HGCP). This study attempts to identify the incidence and clinical significance of HGCP and cribriform carcinoma (CC) by evaluating 114 radical prostatectomy specimens. Cases were divided into three histologic groups for statistical analysis: (1) pure acinar carcinoma: infiltrating acinar carcinoma without evidence of cribriform neoplasia; (2) CC: acinar carcinoma with CC; and (3) HGCP: acinar carcinoma with HGCP. High-grade cribriform prostatic intraepithelial neoplasia was defined as the presence of neoplastic cells spanning the entire lumen in a cribriform configuration in which a basal cell layer could be shown by immunohistochemistry. Similar areas in which no basal cell layer could be seen were diagnosed as CC. The incidence of cribriform neoplasia was 38% (43 of 114). The incidences of HGCP and CC were 13% (15 of 114) and 25% (28 of 114), respectively. Univariate analysis showed a strong association between HGCP and CC both and several preoperative and final pathology results, including digital rectal examination, pathology tumor stage, extraprostatic extension, surgical margin positivity, high Gleason sum (GS), and high tumor volume. Kaplan-Meier analysis showed HGCP to have a 61% cumulative prostate-specific antigen (PSA) failure rate in contrast with CC and pure acinar cancer, which had cumulative PSA failure rates of 15% and 13%, respectively (p = 0.0001, log-rank test). Multivariate Cox's proportional-hazards analysis found preoperative serum PSA, GS, tumor stage, and volume to be important predictors of PSA failure. In a second regression model that included serum PSA, GS, and pathology tumor stage, HGCP was an independent predictor of PSA failure. Both HGCP and CC are closely associated with several poor prognostic indicators, including advanced pathology tumor stage, a high GS, and serum PSA. Multivariate analysis showed HGCP as an independent prognostic indicator. The close association between high tumor volume and HGCP supports the theory that the development of HGCP is a late event in tumor progression, more compatible with the intraductal spread of tumor than dysplasia.

Aged↗
PubMed1995

The incidence of high grade prostatic intraepithelial neoplasia in needle biopsies.

PURPOSE: High grade prostatic intraepithelial neoplasia is the most likely precursor of invasive prostate cancer. The identification of prostatic intraepithelial neoplasia in needle biopsy specimens warrants repeat biopsy because of its high predictive value for cancer. The incidence of prostatic intraepithelial neoplasia in contemporary needle biopsies is unknown. MATERIALS AND METHODS: To determine the incidence of patients requiring repeat needle biopsy because of abnormal findings in needle aspirations (high grade prostatic intraepithelial neoplasia and microscopic foci suspicious for but not diagnostic of malignancy), we compared the pathological findings in 400 prostatic needle biopsies, including 200 consecutive cases from an academic medical center (Mayo Clinic) and an equal number from a private practice laboratory (Glendale Memorial Hospital and Health Center). RESULTS: The biopsies revealed similar findings from the 2 medical centers: benign prostatic tissue in 41.5 to 50% of the cases, prostatic intraepithelial neoplasia in 16.5 to 9.5%, foci suspicious for but not diagnostic of malignancy in 1.5 to 2.5% and cancer in 40.5 to 38% (Mayo Clinic versus Glendale Memorial, respectively). Clinical information was available from the 200 Mayo Clinic patients who underwent biopsy, and there was no difference in the distribution of findings by digital rectal examination or transrectal ultrasound, although the median serum prostate specific antigen concentration was higher in patients with prostatic intraepithelial neoplasia and cancer than in those with benign biopsies. CONCLUSIONS: High grade prostatic intraepithelial neoplasia is a frequent finding in needle biopsies and is present in up to 16.5% of the cases. There was no apparent difference in the incidence of prostatic intraepithelial neoplasia and cancer between 2 geographically diverse medical centers. Up to 18% of patients are candidates for another biopsy based on needle biopsy findings of prostatic intraepithelial neoplasia or foci suspicious for but not diagnostic of malignancy.

Adult↗
PubMed2005

Prostatic intraepithelial neoplasia: a risk factor for prostate cancer.

Prostatic Intraepithelial Neoplasia (PIN) is an increasingly common finding at ultrasound guided prostate biopsy, with the high grade form (HGPIN) thought to be "precancerous". With the more widespread use of extended biopsy protocols, taking sometimes up to 14 cores or more, the incidence of HGPIN can be up to 25%. Histologically, it has many features in common with cancer of the prostate and has been shown to be both associated with cancer at the time of its finding and predictive for the development of prostate cancer in the future. Basic science research has demonstrated genes common specifically to both prostate cancer and HGPIN and immunostaining studies of microvessel density may help to differentiate HGPIN from lower risk PIN. There are no active treatments for HGPIN although there are trials to assess the effectiveness of hormonal therapy and nutritional supplements. Currently most urologists recommend that patients should be followed at 6 monthly intervals with regular PSA and repeat biopsies as indicated.

Adult↗
PubMed1997

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.

Adenocarcinoma↗
PubMed2006

Design and progress of a trial of selenium to prevent prostate cancer among men with high-grade prostatic intraepithelial neoplasia.

High-grade prostatic intraepithelial neoplasia (HGPIN) is generally regarded as a premalignant lesion that progresses toward prostate cancer. In light of the significant sequelae of prostate cancer treatment, prevention is desirable, and men with HGPIN would be suitable, high-risk subjects. There is in vitro, in vivo, epidemiologic, and human experimental evidence that selenium supplementation may protect against prostate cancer. This article introduces the rationale for, and progress to date, of a double-blind, randomized, placebo-controlled trial of selenium supplementation (200 mug/d in the form of selenomethionine), to prevent the development of prostate cancer among men with HGPIN. The trial, Southwest Oncology Group Protocol 9917, funded by a National Cancer Institute program supporting pivotal prevention trials has registered 537 patients and has randomized >380 to date. Subject accrual is expected to be completed by the fall of 2006, with trial completion in 2009.

Adult↗
PubMed2001

Predictive value of total and percent free prostate specific antigen in high grade prostatic intraepithelial neoplasia lesions: results of the Tyrol Prostate Specific Antigen Screening Project.

PURPOSE: We evaluate the predictive values of total and percent free prostate specific antigen (PSA) in regard to high grade intraepithelial lesions in volunteers who participated in the Tyrol PSA Screening Project. MATERIALS AND METHODS: Between June 1995 and December 1998, 1,474 patients undergoing transrectal biopsy of the prostate were evaluated. The primary detection rates of prostate cancer and high grade intraepithelial lesions were evaluated. In addition, the rate of prostate cancer detected on biopsy in patients diagnosed with high grade prostatic intraepithelial neoplasia on the previous biopsy was assessed. Mean total PSA values and mean percent free PSA levels were determined for each study group and compared using the Mann-Whitney U test. RESULTS: A total of 1,077 (73.1%) volunteers had benign prostatic hyperplasia or prostatitis, and 327 (22.2%) had prostate cancer. The primary detection rate for high grade intraepithelial lesions was 4.7% (70 patients) and on repeat biopsy was 38.6% (27). Mean total PSA for the benign prostatic hyperplasia, prostate cancer, high grade and intraepithelial cancer groups were 6.0, 8.7, 5.9 and 5.2 ng./ml., respectively. Mean percent free PSA values for the various groups were 21.9, 12.1, 15.0 and 12.0, respectively. In regard to total PSA there was a statistically significant difference between the prostate cancer and high grade prostatic intraepithelial neoplasia groups (p = 0.016), as well as the prostate cancer and intraepithelial cancer groups (p = 0.028). However, the high grade and intraepithelial cancer groups did not differ significantly. In regard to percent free PSA there were statistically significant differences between the prostate cancer and high grade prostatic intraepithelial neoplasia groups (p = 0.0001), and the high grade and intraepithelial cancer groups (p = 0.013). CONCLUSIONS: In regard to percent free PSA our data indicate a significant difference between high grade intraepithelial lesion and intraepithelial cancer. Due to a substantial overlap in percent free prostate specific antigen between the 2 groups, a clinically useful cutoff point could not be established. Therefore, we recommend repeat biopsy in all patients with high grade intraepithelial lesions regardless of the percent free PSA.

Adult↗
PubMed2000

Prostatic intraepithelial neoplasia.

High-grade prostatic intraepithelial neoplasia (PIN) is now accepted as the most likely pre-invasive stage of adenocarcinoma, a decade after its first formal description. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent invasive carcinoma. The only method of detection is biopsy; PIN does not significantly elevate serum prostate-specific antigen concentration or its derivatives and cannot be detected by ultrasound. Most studies suggest that most patients with PIN will develop carcinoma within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype that are similar to cancer rather than normal prostatic epithelium, indicating impairment of cell differentiation with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.

Humans↗
PubMed2004

High-grade prostatic intraepithelial neoplasia.

High-grade prostatic intraepithelial neoplasia (PIN) is now accepted as the most likely preinvasive stage of adenocarcinoma, almost two decades after its first formal description. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent invasive carcinoma. The only method of detection is biopsy; PIN does not significantly elevate serum prostate-specific antigen (PSA) concentration or its derivatives and cannot be detected by current imaging techniques, including ultrasound. Most patients with PIN will develop carcinoma within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype, which are similar to cancer rather than normal prostatic epithelium, indicating impairment of cell differentiation with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.

Black or African American↗
PubMed2002

Resolution of genotypic heterogeneity in prostate tumors using polymerase chain reaction and comparative genomic hybridization on microdissected carcinoma and prostatic intraepithelial neoplasia foci.

Prostate cancer (CaP) is a multifocal heterogenous disease. A major challenge in CaP research is to identify genetic biomarkers that herald aggressive transformation. To investigate the effect of tumor heterogeneity on the analysis of genomic aberration, we compared the results of comparative genomic hybridization (CGH) analysis of DNA extracted from tumor bulk against that of DNA amplified by degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR) from homogeneous cell population obtained by laser capture microdissection of discrete tumor foci. Sampling by microdissection, aberrations were observed in three of three foci of carcinoma involved with prostatic capsule, and in two of three prostatic intraepithelial neoplasia (PIN) foci examined. Carcinoma foci consistently exhibited more extensive aberrations than the PIN samples obtained from the same tumor. Within these samples, the different tumor foci exhibited gain of 8q, whereas PIN showed no consistent aberration. Using bulk extracted DNA, CGH detected aberrations in only 3 of 21 samples investigated, despite the known trisomy 8 status, as revealed by fluorescence in situ hybridization. The results of this study demonstrate that CGH analysis using bulk dissected fresh tissue is insufficiently sensitive to fully detect the chromosomal numerical aberrations in CaP. Given the considerable intratumor genomic heterogeneity, CGH with microdissection and DOP-PCR amplification provides a more complete repertoire of aberrations as well as a better phenotype-genotype correlation in prostate tumors.

Carcinoma↗
PubMed1996

Progression of prostatic intraepithelial neoplasia to early invasive adenocarcinoma.

OBJECTIVE: High-grade prostatic intraepithelial neoplasia is the most likely precursor of adenocarcinoma. This report describes the diagnostic criteria for prostatic intraepithelial neoplasia, its clinical significance, and the evidence suggesting that it progresses to prostatic adenocarcinoma. METHODS: We reviewed the published evidence linking prostatic intraepithelial neoplasia and prostate cancer. RESULTS: Prostatic intraepithelial neoplasia has a high predictive value as a marker for adenocarcinoma, and its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. Most studies suggest that, if untreated, prostatic intraepithelial neoplasia will progress to early carcinoma, although only indirect evidence exists to support this hypothesis. Androgen deprivation therapy decreases the prevalence and extent of prostatic intraepithelial neoplasia, suggesting that this form of treatment may play a role in chemoprevention. Prostatic intraepithelial neoplasia does not appear to elevate serum PSA concentration. It is associated with progressive abnormalities of phenotype and genotype which are intermediate between normal prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. CONCLUSION: Virtually all data indicate that high-grade prostatic intraepithelial is premalignant, accounting for most if not all cases of prostate cancer.

Adenocarcinoma↗
PubMed2000

Extent and zonal distribution of prostatic intraepithelial neoplasia in patients with prostatic carcinoma in Japan: analysis of whole-mounted prostatectomy specimens.

BACKGROUND: Prostatic intraepithelial neoplasia (PIN), an intraluminar proliferation of epithelial cells in ducts and acini, is divided into high-grade (HGPIN) and low-grade (LGPIN), based on morphologies. HGPIN is considered to be a putative precursor of prostatic adenocarcinoma (PCA). Information on PIN has been limited in Japan, because PIN had not been regarded as a precursor lesion for PCA. METHODS: In this study, extent and zonal distribution of PIN together with its relationship with PCA were examined in totally embedded radical prostatectomy specimens obtained from 70 patients with PCA. Fifty-three patients received androgen deprivation therapy (castrated) and remaining 17 did not (noncastrated). RESULTS: Frequency of HGPIN in noncastrated cases (76%) was much higher than that in castrated cases (26%) (P < 0.001). LGPIN showed the same tendency, but the difference was smaller. Difference in mean number of HGPIN in noncastrated and castrated cases (12.0 and 6.4, respectively) was more marked than in LGPIN (6.4 and 5.1, respectively). Reduction rate of mean size in HGPIN (26%) by the androgen deprivation therapy was larger than in LGPIN. When evaluated in noncastrated cases, the coexistence of PCA and HGPIN was found in 76% of cases in the nontransition and 53% in the transition zone. Close association of PCA and PIN (</=2 mm distance between lesions) was more frequently found in HGPIN (55% of lesions) than in LGPIN (37%) (P < 0.05). Frequency of close association of HGPIN with PCA was 65% in the nontransition and 35% in transition zone. CONCLUSIONS: The present study from Japan supports the etiological importance of HGPIN in the development of PCA. The effect of androgen deprivation therapy is much more marked in HGPIN than in LGPIN.

Adenocarcinoma↗
PubMed2006

High-grade prostatic intraepithelial neoplasia in patients with prostate cancer: MR and MR spectroscopic imaging features--initial experience.

PURPOSE: To retrospectively determine the magnetic resonance (MR) and MR spectroscopic imaging features of high-grade prostatic intraepithelial neoplasia (HGPIN) in patients with prostate cancer. MATERIALS AND METHODS: Approval of the committee on human research was obtained, with a waiver of consent for this HIPAA-compliant study. Endorectal MR imaging and MR spectroscopic imaging were performed in 48 men (mean age, 59 years; range, 47-75 years) prior to radical prostatectomy for prostate cancer. T2-weighted signal intensity and metabolic ratios of peripheral zone HGPIN foci of 6 mm or greater in diameter were recorded by two readers with knowledge of step-section histopathologic findings using areas of confirmed normal and cancerous peripheral zone tissue for comparison. A random effects statistical model was used to compare metabolic ratios from normal, HGPIN, and cancer voxels. RESULTS: A total of 123 peripheral zone HGPIN foci with a mean diameter of 3 mm (range, 1-28 mm) were identified in 37 (77%) patients, but only 20 foci in 14 patients had a diameter of 6 mm or greater. Six foci were excluded, yielding 14 large HGPIN lesions from 11 patients in the final statistical analysis. The larger HGPIN foci were not associated with any focal reduction in T2-weighted signal intensity but demonstrated metabolic findings intermediate between normal and cancerous tissue; the mean ratios of choline (Cho) to creatine (Cr) for normal, HGPIN, and cancer were 0.92, 1.75, and 1.99, respectively, (P < .01), and the corresponding ratios of Cho plus Cr to citrate were 0.34, 0.50, and 0.78 (P < .01). CONCLUSION: HGPIN is metabolically intermediate between normal peripheral zone tissue and prostate cancer at MR spectroscopic imaging but does not manifest any MR imaging abnormality and is rarely of sufficient size to cause substantial error in evaluation of peripheral zone tumor extent in patients with prostate cancer.

Aged↗
PubMed2000

Strategy for repeat biopsy in patients with high grade prostatic intraepithelial neoplasia.

PURPOSE: The finding of high grade prostatic intraepithelial neoplasia in a biopsy specimen without prostate cancer warrants repeat biopsy because of the risk of concurrent cancer. However, to our knowledge the optimal repeat biopsy technique has not yet been defined. We determined the optimal subsequent biopsy strategy for detecting concurrent cancer in patients diagnosed with high grade prostatic intraepithelial neoplasia. MATERIALS AND METHODS: Of 63 men with isolated high grade prostatic intraepithelial neoplasia on initial biopsy 45 underwent repeat biopsy within 1 year. Certain biopsy patterns were used for repeat biopsy, including only the neoplasia site in 8 men, sextant in 12, sextant plus bilateral transition zone in 13 and 11 core multisite directed (sextant, bilateral transition zone, bilateral anterior horn of the peripheral zone and midline peripheral zone) in 12. We compared the location of high grade disease on the initial biopsy with the cancer site on repeat biopsy. RESULTS: Repeat biopsy revealed cancer in 10 of the 45 men (22%), and the sites of high grade prostatic intraepithelial neoplasia and cancer correlated in 6. Cancer was detected at the sextant locations in 9 men. Of the 15 cores positive for cancer 8 were at the original high grade neoplasia site, 6 at a random sextant biopsy site and 1 in the transition zone. High grade disease was discovered bilaterally in 1 man, while prostatic intraepithelial neoplasia and cancer were detected on the same side in the remaining 9. CONCLUSIONS: The optimal repeat biopsy strategy for patients with high grade prostatic intraepithelial neoplasia has not yet been determined but at a minimum it should include targeting the area of known high grade disease and the ipsilateral sextants.

Biopsy↗
PubMed2000

Correlation of increased apoptosis and proliferation with development of prostatic intraepithelial neoplasia (PIN) in ventral prostate of the Noble rat.

BACKGROUND: Imbalance between cell proliferation and cell apoptosis has been considered a key factor in carcinogenesis. Prostatic intraepithelial neoplasia (PIN) is the most likely precancereous lesion and represents the major target for chemoprevention of prostate cancer. The proliferative and apoptotic activities involved in the development of PIN remain to be elucidated. METHODS: Ventral prostates were removed from Noble rats that were treated with a combination of testosterone (T) and estradiol (E(2)) for certain periods of time, and processed for histopathological grading. To evaluate the relationship between cell proliferation and apoptosis, immunohistochemistry for proliferating cell nuclear antigen (PCNA), Ki-67, and in situ DNA nick labeling (TUNEL) for identifying apoptotic cells, were performed on paraffin sections from prostate samples with PIN lesions. The results were correlated with expression patterns of Bcl-2 and Bax, two proteins related to cell survival and cell apoptosis. RESULTS: Pathologically, low-grade PIN (LGPIN) and high-grade PIN (HGPIN) were observed in ducts or alveoli after 3 and 5 months of T + E(2) treatment, respectively. Quantitative evaluation of Ki-67 showed an increased proliferative activity in HGPIN. In contrast to normal prostatic ducts and alveoli, which showed no positive staining for Ki-67 in the nuclei of luminal cells, 25% Ki-67-positive cells were detected in luminal cells of HGPIN. Only 7.5% Ki-67-positive cells were found belonging to the basal cell type. The Ki-67 index showed a higher growth rate from normal to HGPIN. The PCNA results showed a similar expression pattern to that of Ki-67 in normal prostate, LGPIN, and HGPIN. Apoptotic index (number of apoptotic cells/total number of cell counted) was significantly higher (P = 0.028) in HGPIN (3.23%) than in control prostate (1.19%). In contrast to control prostate, which showed no definite expression of Bcl-2, an intense positive expression of Bcl-2 in HGPIN was observed. Positive expression of Bax protein was observed in glandular epithelial cells of normal control prostate and HGPIN as well. CONCLUSIONS: Overexpression of Bcl-2 and higher Ki-67 or PCNA indices in HGPIN suggest that abnormal growth of premalignant lesions might result from an increase in cell proliferation. An increased apoptotic rate in HGPIN further implicates that active apoptosis may accelerate cell turnover in the development of premalignant lesions of the prostate.

Animals↗
PubMed1996

Prostatic intraepithelial neoplasia (PIN) and other prostatic lesions as risk factors and surrogate endpoints for cancer chemoprevention trials.

The most efficient strategy for chemoprevention clinical trials are short-term studies which focus on surrogate endpoint biomarkers (SEBs) in high-risk target populations. High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostate cancer, and is found in a significant number of routine contemporary needle biopsies without cancer. The frequency and extent of PIN are decreased with androgen deprivation therapy, suggesting that it is a suitable endpoint biomarker for modulation. Potential SEBs for screening chemopreventive agents for prostate cancer in short-term Phase II trials include (1) histologic premalignant lesions, such as high-grade PIN; (2) biochemical markers, including prostate-specific antigen (PSA) serum concentration; and (3) morphometric markers, including nuclear texture, shape, and roundness; size and number of nucleoli; and number of apoptotic bodies; (4) proliferation markers, including MIB-1 and PCNA; (5) genetic markers, including nuclear DNA content (ploidy), oncogene c-erbB-2 (HER-2/neu) expression, fluorescence in situ hybridization for chromosome 8; and PSA-producing cells in the blood detected by reverse transcriptase polymerase chain reaction; and (6) differentiation markers, such as microvessel density as a determinant of angiogenesis. Each of these endpoint biomarkers is measured easily and accurately in serum or in tissue specimens such as formalin-fixed, paraffin-embedded needle biopsies, and may be modifiable by intervention. The clinical utility of these biomarkers as modulatable endpoints in prostate cancer chemoprevention needs to be demonstrated in future clinical trials.

Biomarkers↗
PubMed1995

The significance of atypical adenomatous hyperplasia and prostatic intraepithelial neoplasia for the development of prostate carcinoma. An update.

The term prostatic intraepithelial neoplasia (PIN) is an accepted diagnosis in pathology of the prostate. The diagnostic difference between atypical adenomatous hyperplasia (AAH) and adenosis is still under debate. A number of questions remain about the significance of grading of AAH and PIN, the biology of AAH and PIN as precursors of carcinoma, the possibility of treatment of AAH and PIN and whether AAH- and PIN-associated cancers differ from non-associated carcinoma. This paper reviews the results and discussions at the First International Consultation Meeting on Atypical Adenomatous Hyperplasia and Prostatic Intraepithelial Neoplasia and the Origins of the Prostatic Carcinomas. AAH is an architectural atypia of the prostate. The histological and cytological features of AAH are intermediate between BPH and low-grade carcinoma of the prostate. Cell kinetic findings show no distinct neoplastic pattern. AAH may be a precursor of transition zone carcinoma but the findings to date are inconclusive. Follow up studies should address whether the association of AAH and carcinoma is incidental or whether transition occurs between AAH and carcinoma. In contrast, PIN is an accepted preneoplastic lesion and the most likely precursor of the dorso-peripheral zone carcinoma. The diagnosis of high-grade PIN is clinically important, because high-grade PIN is associated with carcinoma in a high percentage of patients (38-100%). AAH- and PIN-associated cancers may not differ from other prostatic cancers. At present treatment for AAH and PIN without carcinoma is not indicated, but high-grade PIN warrants surveillance and follow up of the patient to identify a possible coexisting cancer. It must be stressed that AAH and PIN are multifocal lesions and both are age-associated.

Carcinoma↗
PubMed2000

Structural changes and alteration in expression of TGF-beta1 and its receptors in prostatic intraepithelial neoplasia (PIN) in the ventral prostate of noble rats.

BACKGROUND: Prostatic intraepithelial neoplasia (PIN) is the most likely pre-cancereous lesion and represents the major target for chemoprevention of prostate cancer. The multi-functional role of TGF-beta1, together with its receptors, in normal prostate and development of prostatic neoplasia remains controversial and requires further investigation. METHODS: Ventral prostates were removed from Noble rats treated with a combination of testosterone (T) and estradiol (E(2)) for various periods of time, and processed for ultrastructural examination and histopathological grading. To evaluate the role of TGF-beta1 and TGFbeta receptor types I and II in normal prostate and high-grade PIN development, expression pattern of TGF-beta1 and TGFbeta-RI and TGFbeta-RII were studied on prostate samples with PIN lesions. RESULTS: Pathologically, low-grade PIN (LGPIN) and high-grade PIN (HGPIN) were observed in ducts or alveoli after three and five months of T + E(2) treatment, respectively. EM study revealed that HGPIN cells were characterized by a reduction in abundance of secretory apparatus and the nucleus with highly irregular and undulated membrane and often with inclusion bodies although the basal lamina remained largely normal. This was associated with a high level of expression of TGF-beta1 in stromal tissue subjacent to foci of HGPIN. No definite positive reactivity of TGF-beta1 was identified in glandular epithelial cells of HGPIN. These results implicated that the major site for the TGF-beta1 production remained to be restricted to stromal compartment at the stage of HGPIN, and a paracrine regulation of TGF-beta1 might be involved in the development of HGPIN. Positive staining for the TGFbeta-RI was found in the cytoplasm of luminal epithelial cells of normal ventral prostate. The intense positive reactivity for TGFbeta-RI was also identified in prostates with HGPIN lesions. Similar expression pattern of TGFbeta-RII was also observed. CONCLUSIONS: Based on the EM study, we concluded that HGPIN in ventral prostate was accompanied with alterations in nuclear morphology together with a change in secretory activity. The over expression of TGFbeta-RI and RII in HGPIN cells as well as TGF-beta1 in stromal tissue subjacent to HGPIN implicated a growth-stimulating role instead of inhibiting role of this peptide growth factor during the early stage of prostatic neoplasia.

Animals↗