Malignant Prostatic Lesions Research Articles

Malignant lesions in the ventral prostate of alloxan‐induced diabetic rats

The aim of this study was to evaluate the changes caused by chronic diabetes in the rat ventral prostate and to establish a correlation between diabetes and the development of prostatic lesions. Male rats received alloxan (42 mg/kg b.w.) to induce diabetes. Ninety days after diabetes diagnosis, animals were sacrificed and the ventral prostate was removed and prepared for general and immunohistochemical analyses. The total area showing different types of lesions was estimated. Diabetes led to a decrease in the body and prostatic weights, as well as in testosterone levels. The prostate morphology and stereology showed high variation in the diabetic group. Some animals had light changes; the great majority had an intense epithelial atrophy; and other rats showed premalignant and malignant lesions in the prostate. Such epithelial atrophy was, in some samples, combined with chronic inflammation, similar to proliferative inflammatory atrophy (PIA). The diabetic group also presented high incidence of prostatitis, adenocarcinoma and prostatic intra-epithelial neoplasia (PIN). Samples with adenocarcinoma had poorly differentiated acini with high levels of cellular proliferation and nuclear atypia. These lesions exhibited an invasive feature showing Bcl-2-positive cells and interruptions in the basement membrane. An association of PIA, PIN and adenocarcinoma was detected in one sample. Reduced androgen levels have a synergic effect to insulin dysfunction promoting negative effects in the rat prostate. Diabetic individuals had a high incidence of prostatitis, and this inflammation could stimulate the incidence of other forms of prostatic pathology.

Piezoelectricity and prostate cancer: Proposed interaction between electromagnetic field and prostatic crystalloids

There is evidence that electromagnetic fields (EMF) play some part in the pathogenesis of prostate cancer, but the pathogenic mechanism remains unknown. The normal prostate gland and both benign and malignant prostate lesions contain abundant calcium/phosphorus crystalloids with various morphologies, which seem to be heterogeneously and diffusely distributed within the gland. We hypothesize that an environmental EMF may result in simultaneous, multidirectional and diffuse compression or expansion of these crystalloids (a piezoelectric effect). This would result in a slight mechanical distortion of the prostate, potentially altering cell behavior and enhancing the expression of specific genes, particularly those involved in suppressing apoptosis. A mathematical model of the cell mechanical effect is presented, and the hypothesis is related to current clinical evidence and to potential validation by critical laboratory tests.

EMPIRICAL DESCRIPTION OF MR ENHANCEMENT PATTERNS AS A MEANS TO DIFFERENTIATE BETWEEN MALIGNANT PROSTATE LESIONS AND NORMAL PERIPHERAL ZONE

You have accessJournal of Urology1 Apr 2008EMPIRICAL DESCRIPTION OF MR ENHANCEMENT PATTERNS AS A MEANS TO DIFFERENTIATE BETWEEN MALIGNANT PROSTATE LESIONS AND NORMAL PERIPHERAL ZONE Bashar Zelhof, Martin Lowry, Greta Rodrigues, Sigurd Kraus, and Lindsay W Turnbull Bashar ZelhofBashar Zelhof More articles by this author , Martin LowryMartin Lowry More articles by this author , Greta RodriguesGreta Rodrigues More articles by this author , Sigurd KrausSigurd Kraus More articles by this author , and Lindsay W TurnbullLindsay W Turnbull More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(08)61996-5AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "EMPIRICAL DESCRIPTION OF MR ENHANCEMENT PATTERNS AS A MEANS TO DIFFERENTIATE BETWEEN MALIGNANT PROSTATE LESIONS AND NORMAL PERIPHERAL ZONE." The Journal of Urology, 179(4S), pp. 683–684 © 2008 by American Urological AssociationFiguresReferencesRelatedDetails Volume 179Issue 4SApril 2008Page: 683-684 Advertisement Copyright & Permissions© 2008 by American Urological AssociationMetricsAuthor Information Bashar Zelhof More articles by this author Martin Lowry More articles by this author Greta Rodrigues More articles by this author Sigurd Kraus More articles by this author Lindsay W Turnbull More articles by this author Expand All Advertisement PDF DownloadLoading ...

The Utility of Transrectal Real-Time Elastography in the Diagnosis of Prostate Cancer

The aim of this study is to evaluate the diagnostic performance of transrectal real-time elastography (TRTE) to differentiate benign from malignant prostatic lesions, with pathologic diagnosis obtained by prostatic needle biopsy. Conventional gray scale transrectal ultrasonography (TRUS) and power Doppler ultrasonography (PDUS) were performed in 107 men who had elevated serum prostate-specific antigen level >4 ng/mL or abnormal findings on digital rectal examination. For baseline TRUS and PDUS imaging, the suspicion of carcinoma was scored using previously proposed five-point subjective scale. For TRTE imaging, we used newly adopted five-point subjective scale based on the degree and distribution of strain in relation to hypoechoic area, which simultaneously displayed on B-mode image. All patients underwent transperineal systematic 8-cores biopsies, as well as up to four cores of targeted biopsy from suspicious area by TRUS, PDUS and/or TRTE. The samples were diagnosed pathologically and compared with the findings of TRUS, PDUS and TRTE. Prostate cancer was detected in 40 (37%) of 107 patients. When a cutoff point of 3 (displaying focal asymmetric lesion without strain not related to hypoechoic lesion) was used, TRTE had 68% sensitivity, 81% specificity and 76% accuracy. TRTE was comparable with PDUS (70% sensitivity, 75% specificity and 73% accuracy) and had significantly higher sensitivity than TRUS (68% vs. 50%, p = 0.027). Combination of TRTE with PDUS increased sensitivity to 78%. The detection rate of directed biopsy from suspicious area in either TRTE or PDUS (TRTE+PDUS–directed biopsy) was 29% (31/107) by patient and was comparable with systematic biopsy (31%, 33/107, p = 0.86), whereas the detection rate of TRTE+PDUS–directed biopsy by core (55/111, 50%) was significantly higher than systematic biopsy (132/856, 15%, p < 0.0001). For assessing prostatic lesions, TRTE with B-mode image-based scoring had almost the same diagnostic performance as PDUS. Although TRTE+PDUS–directed biopsy detected comparable number of cancers with systematic biopsy, both techniques should be used supplementarily for minimizing the number of missing cancers. (E-mail: kamoi@koto.kpu-m.ac.jp)

Immunophenotypic characterization of benign and malignant prostatic lesions

Background: Biopsy diagnosis is the gold standard for differentiating benign and malignant prostatic enlargements. This study was aimed at supplementing biopsy diagnosis with immunophenotypic characters of prostatic lesions. Methods: Twenty five cases each of nodular hyperplasia and adenocarcinoma prostate were compared for their morphologic appearances and immunophenotyping, by studying antibodies to prostate specific antigen (PSA), transglutaminase, chromogranin and high molecular weight keratin, proliferating cell nuclear antigen, cell death (apoptosis) and neovascularisation (CD 34). Results: Markers of differentiation (PSA and transglutaminase) aided recognition of higher-grade tumours. PSA negativity avoided metaplasia being overcalled as carcinoma. Loss of basal cells around malignant prostatic acini as determined by high molecular weight keratin (HMWK), was useful in foci of atypical small acinar proliferation and in prostatic intraepithelial neoplasia. Assessment of proliferation indices identified subsets of tumours, within conventional morphologic Gleason's grades, with a higher growth fraction. Cell death determination and study of tumour vessels did not offer any improvement on morphology. Conclusion: Immunophenotypic assessment helps in refining morphologic diagnosis of prostatic lesions. Differentiation and proliferation markers objectively assess tumour characteristics with their biologic growth potential and are recommended for diagnostic use.They also help in assessement of response to therapy.

TMPRSS2-ERG Fusion Prostate Cancer: An Early Molecular Event Associated With Invasion

Prostate cancer (PCA) is one of the most prevalent cancers and a major leading cause of morbidity and mortality in the Western world. The TMPRSS2-ERG fusion was recently identified as a common recurrent chromosomal aberration in this malignancy. In our study, we interrogated a broad spectrum of benign, precursor, and malignant prostatic lesions to assess the TMPRSS2-ERG fusion status using a multicolor interphase fluorescence in situ hybridization assay. Samples from hospital-based cohorts consisted of 237 clinically localized PCA, 34 hormone naive metastases, 9 hormone refractory metastases, 26 high grade prostatic intraepithelial neoplasia lesions, 15 samples of benign prostatic hyperplasia, 38 of proliferative inflammatory atrophy, and 47 of benign prostatic tissue. The TMPRSS2-ERG fusion was present in 48.5% of clinically localized PCA, 30% of hormone naive metastases, 33% of hormone refractory metastases, and in 19% of high grade prostatic intraepithelial neoplasia lesions in intermingling to cancer foci. Almost all these fusion positive cases show a homogenous distribution of the fusion pattern. In contrast, none of the other samples harbored this genetic aberration. If we consider the high incidence of PCA and the high frequency of this gene fusion, TMPRSS2-ERG is the most common genetic aberration so far described in human malignancies. Furthermore, its clinical application as a biomarker and ancillary diagnostic test is promising given its high specificity.

Human telomerase and α-methylacyl-coenzyme A racemase in prostatic carcinoma. A comparative immunohistochemical study

Human telomerase detected by in situ hybridization has been demonstrated to be a useful tool for the diagnosis of malignancy and has also been tested by reverse transcriptase-polymerase chain reaction in several tumors such as hepatic cell carcinoma, melanoma, colonic carcinoma, gastric carcinoma, biliary carcinoma, breast carcinoma, mesothelioma, lung carcinoma, female tract carcinoma, and prostatic carcinoma. A monoclonal antibody (clone Tel-24) that allows for the detection of human telomerase reverse transcriptase (hTERT) in paraffin blocks of archival material has recently been developed. Carcinomas of cervix, endometrium, and breast have been studied by this method, but its value in prostatic carcinoma has not been explored; for that reason, we studied benign and malignant prostatic lesions by immunohistochemistry using paraffin embedded tissue. The aim of the study was to define the sensitivity and specificity of hTERT in prostate cancer, in comparison with alpha-methylacyl-coenzyme A racemase (AMACR) (P504-S). Fifty-five specimens of diverse prostatic lesions were selected for study (43 needle biopsies and 12 transurethral resections); there were 61 malignancies (47 infiltrating carcinomas and 14 high-grade prostatic intraepithelial neoplasias [PIN]) and 29 benign lesions (10 basal cell hyperplasias, 12 nodular hyperplasias, 4 chronic prostatitis, and 3 atrophic glands). Signal for hTERT nucleolar was detected in 31 of 47 infiltrating adenocarcinomas, in 11 of 14 PIN, and in none of 27 benign lesions (sensitivity, 71%; specificity, 100%). Diffuse cytoplasmic positivity for AMACR was found in 37 of 41 infiltrating adenocarcinomas, in 7 of 7 PIN, and in 6 of 22 benign lesions (sensitivity, 91%; specificity, 72%). These results indicate that hTERT is highly specific of malignancy, with no false-positive cases; however, it had lower sensitivity than AMACR.

Toremifene – a promising therapy for the prevention of prostate cancer and complications of androgen deprivation therapy

Deregulation of the estrogen axis in humans prompts a series of tissue-specific events. In the breast and prostate, alterations in estrogen signalling lead to genotypic and phenotypic molecular alterations that result in dysplastic cellular appearance, deregulated cell growth and carcinoma. In bone, decreased estrogen leads to increased osteoclastogenesis and bone resorption, decreased bone mineral density and a significant fracture risk. Toremifene is a selective estrogen receptor modulator that exerts pharmacological activity in the breast, bone and prostate. An intense interest in developing this agent for prostate cancer chemoprevention is based on the reduction of premalignant and malignant prostate lesions in a transgenic model of prostate cancer. Biological and clinical activity was demonstrated in Phase II trials by the prevention of progression to prostate cancer in men with high-grade prostate intraepithelial neoplasia and through suppression of bone turnover biomarkers and increased bone mineral density in men on androgen deprivation therapy for prostate cancer.

Diffusion-weighted magnetic resonance imaging and its application to cancer

Diffusion-weighted magnetic resonance imaging (DW-MRI) provides image contrast through measurement of the diffusion properties of water within tissues. Application of diffusion sensitising gradients to the MR pulse sequence allows water molecular displacement over distances of 1–20 μm to be recognised. Diffusion can be predominantly unidirectional (anisotropic) or not (isotropic). Combining images obtained with different amounts of diffusion weighting provides an apparent diffusion coefficient (ADC) map. In cancer imaging DW-MRI has been used to distinguish brain tumours from peritumoural oedema. It is also increasingly exploited to differentiate benign and malignant lesions in liver, breast and prostate where increased cellularity of malignant lesions restricts water motion in a reduced extracellular space. It is proving valuable in monitoring treatment where changes due to cell swelling and apoptosis are measurable as changes in ADC at an earlier stage than subsequent conventional radiological response indicators.

Transrectal ultrasonography for the early diagnosis of adenocarcinoma of the prostate: a new maneuver designed to improve the differentiation of malignant and benign lesions.

Transrectal ultrasound can reveal potentially malignant prostate lesions while they are still small. However, based on ultrasound alone they are often difficult to distinguish from benign focal lesions. We tested the reliability of a new technique for the sonographic evaluation of typical prostate lesions in differentiating adenocarcinoma from benign lesions. During 18 months 398 consecutive male patients 45 to 76 years old underwent transrectal ultrasound for the early detection of prostate cancer. When suspicious hypoechoic lesions were noted in the peripheral regions of the prostate, moderate pressure was applied on the lesion using the ultrasound probe to evaluate consistency. Based on the response lesions were classified as deformable (the shape changed from approximately spherical to oval) or nondeformable (the original shape was retained). All lesions were then diagnosed based on fine needle biopsy. Peripheral hypoechoic prostate lesions were sonographically identified in 146 of 398 patients (36.7%). In 68 cases nondeformable lesions proved to be adenocarcinoma in 63 (92.6%), and chronic prostatitis and/or adenomatous hyperplasia in 5. In contrast, 62 of the 78 deformable nodules (79.5%) showed histological features of hyperplasia and/or chronic inflammation. The remaining 16 nodules, which showed more limited changes in shape during compression, were characterized by hyperplasia with acute inflammatory changes. In 5 cases there was also evidence of adenocarcinoma. Ultrasound guided compression of suspicious prostate lesions detected on transrectal sonography is a simple, rapid and reliable maneuver that may increase the diagnostic potential of this examination.

Expression‐patterns of the RNA component (hTR)and the catalytic subunit (hTERT) of human telomerase in nonneoplastic prostate tissue, prostatic intraepithelial neoplasia, and prostate cancer

Telomerase, a ribonucleoprotein, is composed of a RNA component (hTR) and two protein subunits. One of these subunits, the catalytic subunit (human telomerase reverse transcriptase, hTERT), represents a reverse transcriptase. hTERT-expression is closely correlated with telomerase activity. The telomerase is thought to be involved in immortalization process. By adding hexamic repeats to the end of chromosomal DNA, the telomeres, the enzyme is able to stop progresssive telomeric DNA loss that occurs during cell division due to the end replication problem that stops the mitotic clock. Expression-patterns of hTR using radioactive in situ hybridization with (35)S-labelled RNA probes were compared with immunhistochemical staining for hTERT in 14 cases of archival paraffin-embedded samples of normal prostatic tissue, high-grade prostatic intraepithelial neoplasia (PIN), prostatic cancer, and one atypical adenomatous hyperplasia (AAH). Beside the expression-patterns each telomerase component was evaluated semiquantitatively. hTERT and hTR can be found in nonneoplstic tissue and are upregulated in premalignant transformated lesions. AAH showed no hTERT-expression and low hTR-expression. There is a heterogenous expression within prostatic carcinomas. No association was observed between the grade of the tumour differentiation and semiquantitative levels of hTR- or hTERT-expression. Telomerase is of limited value for the diagnostic of malignant or benign lesions in prostate.

Differential diagnosis of prostate lesions with the use of biomagnetic measurements and non-linear analysis.

The purpose of this study was to investigate the biomagnetic activity emitted from the prostate gland and to differentiate cancerous from benign prostate lesions with the use of biomagnetic measurement and non-linear analysis. Magnetic recordings were obtained from 47 patients with palpable prostate lesions. Histology revealed 24 prostate cancer patients and 23 benign prostate hyperplasia (BPH) patients. The superconducting quantum interference device (SQUID) biomagnetometer was used to measure the prostate's magnetic field by placing the SQUID detector 3 mm above the symphysis pubis. The magnetic field recorded in the 2-7 Hz frequency range was of high amplitude in most malignant lesions whereas all benign cases were of low amplitude. According to our results, the sensitivity, specificity, positive predictive value and negative predictive value were 83.33%, 100%, 100% and 85.18%, respectively. By applying the Grassberger-Procaccia algorithm to the magnetoprostatogram time series in malignant and benign prostate lesions we found clear saturation in malignant prostate lesions with m>7 whereas in the benign lesions there was not clear saturation. Prostate cancer emits higher biomagnetic activity than the BPH. This confirms a higher angiogenic activity in prostate cancer than the BPH lesions. Furthermore, the saturation value in the estimation of the correlation dimension of the attractor for the cancer lesions confirms the lower complexity of the system in comparison to the BPH, which is characterized by higher complexity.

Lesiones prostáticas neoplásicas y no neoplásicas con células claras

A variety of prostatic lesions may be consituted by clear cells and the differential diagnosis under these conditions is wide. The cytoplasm may become clear for several reasons such as: accumulation of glycogen and fat, increase of water, and dilatation of sub-cellular organelles.The differential diagnosis includes a multiplicity of benign and malignant prostatic lesions as: clear cells cribriform hyperplasia, sclerosing adenosis, atypical adenomatous hyperplasia and other cancer mimics. These conditions are discussed and illustrated in the present paper.

Utility of immunohistochemical detection of prostate-specific Ets for the diagnosis of benign and malignant prostatic epithelial lesions.

Human prostate-specific Ets (hPSE) belongs to the Ets family. It regulates the proliferation, differentiation, and development of prostate epithelial cells. A recent study showed that hPSE can be detected in normal glands but not in cell lines established from prostate cancer (PCA), suggesting a translational disorder of hPSE from mRNA to protein in PCA. Immunohistochemical detection of hPSE could therefore be another method of differential diagnosis of PCA from other proliferative conditions in the prostate. An immunohistochemical detection of hPSE was carried out on the whole mounted prostatectomy specimen obtained from 19 cases with PCA. Basal and secretory luminar cells showed a diffuse cytoplasmic staining for hPSE in normal glands, hyperplastic glands, and prostate intraepithelial neoplasia lesions. Whereas approximately 30% of PCA lesions showed a negative staining for hPSE, the positive rate for hPSE between PCA and benign glands or prostate intraepithelial neoplasia (PIN), was statistically significant (P < 0.05). Staining intensities in normal glands, hyperplastic glands, and PIN lesions were similar, but generally stronger than those in PCA lesions. Negative immunoreactivity for hPSE strongly suggests malignancy in the prostate glands. Decreased immunoreactivities of glands for hPSE could suggest PCA.

Antiproliferative B cell translocation gene 2 protein is down-regulated post-transcriptionally as an early event in prostate carcinogenesis.

B cell translocation gene 2 (BTG2) is a p53 target that negatively regulates cell cycle progression in response to DNA damage and other stress. The objective of this study was to examine the expression, regulation and tumor suppressor properties of BTG2 in prostate cells. By immunohistochemistry BTG2 protein was detected in approximately 50% of basal cells in benign glands from the peripheral zone of the human prostate. BTG2 was expressed in all hyperproliferative atrophic peripheral zone lesions examined (simple atrophy, post-atrophic hyperplasia and proliferative inflammatory atrophy), but was undetectable or detectable at very low levels in the hyperproliferative epithelial cells of HGPIN and prostate cancer. BTG2 mRNA was detected in non-malignant prostate epithelial (PE) cells and in LNCaP cells, but not in PC-3 cells, consistent with p53-dependent regulation. In PE cells BTG2 protein was detected in areas of cell confluence by immunohistochemistry. BTG2 protein in LNCaP cells was undetectable by immunohistochemistry but was detected by immunoblotting at 8- to 9-fold lower levels than in PE cells. BTG2 protein levels were shown to be regulated by the ubiquitin-proteosome system. Forced expression of BTG2 in PC-3 cells was accompanied by a decreased rate of cell proliferation and decreased tumorigenicity of these cells in vivo. Taken together, these findings suggest that BTG2 functions as a tumor suppressor in prostate cells that is activated by cell quiescence, cell growth stimuli as part of a positive feedback mechanism and in response to DNA damage or other cell stress. The low steady-state levels of BTG2 protein in HGPIN and prostate cancer, a potential consequence of increased proteosomal degradation, may have important implications in the initiation and progression of malignant prostate lesions. Furthermore, these findings suggest that a significant component of the p53 G(1) arrest pathway might be inactivated in prostate cancer even in the absence of genetic mutations in p53.

CD40 is not detected on human prostate cancer cells by immunohistologic techniques

Objectives. The CD40 antigen is expressed by antigen-presenting cells, many kinds of epithelium, and carcinomas. As signaling through CD40 modulates the differentiation state of CD40-expressing cells, we wanted to investigate whether benign or malignant prostate epithelium expressed CD40. Methods. Twenty-two paraffin-embedded and 10 snap-frozen human prostate tissue samples were analyzed by immunohistologic methods, using the basal cell-specific markers, high molecular weight cytokeratin (HMWCK) and keratin-14 (K14), and the luminal cell marker, low molecular weight cytokeratin (LMWCK), together with CD40. Fresh prostate tissue was cultured in vitro and analyzed by immunocytofluorescence. Results. The pattern of CD40 expression was continuous on basal epithelial cells of normal and hyperplastic prostate glands but discontinuous in glands that featured prostatic intraepithelial neoplasia. Coexpression of CD40 with the basal cell-specific cytokeratins, HMWCK and K14, was confirmed by double labeling. In contrast, glandular epithelial cells in prostate adenocarcinoma did not express CD40 or these cytokeratins. A luminal cell phenotype defined as CAM5.2-positive and HMWCK-negative K14-negative was identified among primary epithelial cells cultured in vitro. Most of the cultured cells (more than 99%) were also CD40-negative. Conclusions. Together, our results support the hypothesis that CD40 expression correlates with the basal cell phenotype, which is lost upon malignant transformation of the prostate. Hence, CD40 may be useful diagnostically to distinguish benign from malignant prostate lesions in biopsy material.

P63 Is a Prostate Basal Cell Marker and Is Required for Prostate Development

The p53 homologue p63 encodes for different isotypes able to either transactivate p53 reporter genes (TAp63) or act as p53-dominant-negatives (DeltaNp63). p63 is expressed in the basal cells of many epithelial organs and its germline inactivation in the mouse results in agenesis of organs such as skin appendages and the breast. Here, we show that prostate basal cells, but not secretory or neuroendocrine cells, express p63. In addition, prostate basal cells in culture predominantly express the DeltaNp63alpha isotype. In contrast, p63 protein is not detected in human prostate adenocarcinomas. Finally, and most importantly, p63(-/-) mice do not develop the prostate. These results indicate that p63 is required for prostate development and support the hypothesis that basal cells represent and/or include prostate stem cells. Furthermore, our results show that p63 immunohistochemistry may be a valuable tool in the differential diagnosis of benign versus malignant prostatic lesions.

The value of prostatic specific antigen density in the early diagnosis of prostate cancer.

In order to differentiate benign from malignant prostatic lesions, 42 patients were evaluated using the prostate specific antigen density (PSAD) test. All patients were evaluated with PSA determination, digital rectal examination (DRE), transrectal ultrasonography (TRUS) and ultrasound-guided prostatic biopsies. PSA was analyzed by the I-MX ABBOT assay. PSAD was determined by dividing the serum PSA by the volume of the prostate. Prostatic biopsies identified cancer in 3 of the 42 patients (6.38%). It is concluded that PSAD is valuable for the early diagnosis of localized prostatic carcinoma, especially when there are negative findings from DRE and/or TRUS.

Allelic loss of 8p sequences in prostatic intraepithelial neoplasia and carcinoma

Objectives Previous work has suggested that prostatic intraepithelial neoplasia (PIN) may be a premalignant lesion important in tumorigenesis of the prostate. However, to adequately test this hypothesis at the genetic level, it is necessary to determine whether lesions in close proximity demonstrate similar genetic alterations and, hence, whether an “evolutionary” relationship might exist between PIN and tumor in the same prostate. Therefore, the purpose of this study was to examine at least two PIN lesions per prostate (one adjacent to and another distant from malignant lesions in the same prostate) for similarities or differences in the types and frequencies of genetic alterations. Methods To accomplish this goal, DNA was extracted from microdissected PIN, tumor and normal epithelial tissue samples from 48 radical prostatectomies and amplified using polymerase chain reaction techniques at highly polymorphic microsatellite repeat sequences at proximal ( D8S87, 8p12) and distal ( NEFL, 8p21) loci on the short arm of chromosome 8. PIN specimens were either adjacent to (within one high-power microscopic field [HPF]) or distant from (separated by two or more HPFs) tumor specimens from the same patients. Results Similar fractional allelic loss frequencies were observed for informative tumor (10 [35%] of 29) and PIN (6 [21%] of 29) samples at the NEFL locus, but allelic loss at the D8S87 locus was observed only in tumors (8 [22%] of 36 informative samples). Moreover, allelic loss at the NEFL locus involved the same allele in 4 cases and different alleles in 3 cases. Interestingly, all 4 cases with the same allele loss were from adjacent PIN and tumor tissues and all 3 with different allele loss were from distant PIN and tumor. Conclusions These results suggest that PIN and invasive cancer share common genetic events (eg, deletion at the NEFL locus) along the same pathway of development in the prostrate.

Stereological estimation of nucleolar organizer regions in prostatic tissue with an optical disector

Silver-stained nucleolar organizer regions (AgNORs) were studied in 10 hyperplastic, 10 inflamed, nine prostatic intraepithelial neoplastic (PIN) and 20 malignant prostatic lesions. Optical disector measurement on 15 micron sections showed that upper frequency limits for 1.5 microns and 2.0 microns AgNOR particles were 10% and 2% in benign lesions and 18% and 9% in PIN. Using these cut-off values for diagnosis we found a low sensitivity and high specificity in distinguishing benign lesions from PIN and PIN from carcinoma. A high sensitivity and high specificity were obtained in separating benign lesions from carcinoma. AgNOR typing on routine "two-dimensional" sections showed that upper frequency limits for types B2, B3 and C2 were 25%, 3% and 0% in benign lesions and 38%, 23% and 11% in PIN. Using these cut-off values for diagnosis we found lower sensitivity and specificity values among all the differential diagnostic categories. We conclude that although both methods may contribute to the differential diagnosis between benign and malignant prostatic lesions, stereological estimation was a technically simple method, ensuring unbiased sampling and resulting in higher sensitivity and specificity. It may thus prove helpful in the differentiation of borderline cases in routine diagnostic pathology.