bromochloroacetic-acid and Prostatic-Intraepithelial-Neoplasia

Small acinar lesions of the prostate may mimic prostate cancer. In the central and transition zone of the prostate, atypical adenomatous hyperplasia (AAH) must be differentiated from low grade carcinoma (Gleason score 2-5). In the dorso-peripheral zone, high grade prostatic intraepithelial neoplasia (PIN) and atypical small acinar proliferations (ASAP) are the most important lesions mimicking carcinoma. Further differentiation is necessary between high grade PIN and intraductal carcinoma. ASAP, on the other hand, may mimic low grade carcinoma. The significance of basal cell type cytokeratin immunohistochemistry (IHC) in the differentiation between ASAP and low grade carcinoma of the prostate was substantiated by additional MIB-1 IHC. The status of the basal cell layer in ASAP was found to be variable (complete, fragmented and absent). Independent of the status of the basal cell layer, the mean MIB-1 proliferation index of ASAP was significantly higher than that of clearly benign lesions and did not differ from that of low grade carcinoma. As carcinoma is frequently detected in rebiopsies, close clinical follow up of patients with ASAP is advisable.

Topics: Antigens, Nuclear; Biomarkers, Tumor; Carcinoma, Acinar Cell; Cell Division; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Nuclear Proteins; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

A variety of small acinar lesions of the prostate can mimic prostate cancer in punch biopsies and in transurethral resection material. The first part of this review deals with differential diagnostic problems of the central and transition zone, including atypical adenomatous hyperplasia of the prostate, atrophic processes, sclerosing adenosis, basal cell hyperplasia, and low-grade adenocarcinoma. The second part deals with differential diagnostic problems in the peripheral zone: prostatic intraepithelial neoplasia, postatrophic hyperplasia, Cowper's glands, seminal vesicles, and ductal and intraductal carcinoma. Finally, atypical and small acinar proliferations are described. Diagnostic perspectives are discussed. proliferations (ASAP) that cannot be integrated into any of the well-established diagnostic entities [1, 16, 22, 41]. The relevant glandular proliferations of the central, transitional and peripheral zones of the prostate are discussed here with reference to the related carcinomas.

Topics: Adenocarcinoma; Atrophy; Diagnosis, Differential; Humans; Keratins; Male; Precancerous Conditions; Prostate; Prostate-Specific Antigen; Prostatic Diseases; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

Existing clinical data have shown that high-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precursor to prostate cancer (CaP). Criteria to distinguish HGPIN that progress to CaP from those that do not remain poorly defined. Our objective was to evaluate microvessel density as a molecular marker for distinguishing HGPINs that have the potential of progressing to cancer.. Human prostatic tissue samples were collected randomly from 50 prostatectomy and cystoprostatectomy patients. Formalin-fixed and paraffin-embedded sections were used for immunohistochemical localization of rabbit anti-human von Willebrand factor VIII (vWF) IgG, mouse anti-high molecular weight cytokeratin 34BE-12 in basal cells, and mouse anti-heparan sulphate proteoglycan (HSPG) IgGs in basement membranes associated with benign prostatic hyperplasia (BPH), PIN associated with some BPH (isolated PIN), and PIN associated with CaP.. Analysis of immunostaining data showed that PINs could be categorized according to their distributions within and outside 2 standard deviations (SD) of the mean for microvessel density. The average number of microvessels was significantly higher (P < 0.0001) in PINs associated with Gleason score 7 tumors than those associated with Gleason scores 4-6 (P < 0.1328) or 8 and 9 tumors (P < 0.1708). Morphologically, PINs within 2 SD were composed of low- and high-grade type, whereas those outside 2 SD of microvessel density were predominantly of high-grade type. Cytokeratin and HSPG localization patterns also showed differences in PINs found within and outside 2 SD of microvessel density. We found localization of cytokeratin 34BE-12 in basal cells of specimens with BPH alone, isolated PIN, and PIN associated with CaP within 2 SD, whereas many PINs outside 2 SD showed disruptions in cytokeratin localization. The basement membranes of PINs within 2 SD of microvessel density were relatively intact, whereas those outside 2 SD were fragmented.. Our immunostaining data indicates that once HGPIN is found in the initial prostatic biopsy, it should be evaluated for microvessel density by localization of vWF. Our data indicate that characteristics of HGPIN can be augmented by evaluations of cytokeratin and HSPG molecular markers to assess the potential of HGPIN progression to malignancy. When biopsy samples show HGPIN with increased microvessel density and disrupted cytokeratin and HSPG markers, the patient may be a candidate for repeat biopsy. Since our study is limited to 50 prostate tissue samples, we emphasize that our conclusion is tentative and ought to be confirmed in a study with a larger sample size. This is the first report to show that microvessel density may distinguish HGPIN that is a precursor to prostate cancer.

Topics: Aged; Biomarkers, Tumor; Disease Progression; Heparan Sulfate Proteoglycans; Humans; Immunoenzyme Techniques; Keratins; Male; Microcirculation; Middle Aged; Neovascularization, Pathologic; Prostatectomy; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Urinary Bladder Neoplasms; von Willebrand Factor

To describe the morphology of focal prostatic atrophy and propose a comprehensive histologic classification for a proper diagnostic recognition.. A broad immunohistochemical study was performed as an adjunct to its recognition as well as a contribution to pathogenesis.. A morphologic continuum was seen on needle biopsies. Chronic inflammation was present only in complete atrophy. Immunohistochemical findings in partial atrophy are similar to normal acini. Luminal compartment in complete atrophy shows aberrant expression of 34betaE12 favoring an intermediate phenotype. ERG negativity in all variants of atrophy may have value in the identification of the lesion.. The morphologic findings favor a continuum probably partially preceding complete atrophy. Chronic inflammation may be a secondary phenomenon seen only in complete atrophy. Overexpression in complete atrophy of glutathione S-transferase pi relates to oxidative stress possibly related to chronic ischemia, of c-Met favors the concept that intermediate cells may be target for carcinogenesis, and of CD44 may be related to the recruitment of inflammatory cells.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Atrophy; Biopsy, Needle; Diagnosis, Differential; Humans; Hyaluronan Receptors; Immunohistochemistry; Kallikreins; Keratins; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Diseases; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Sclerosis

To develop and validate a technique for construction of intermediate density tissue microarray (TMA) slides based on the transfer of tissue from pre-existing routine slides provided for pathology diagnosis with validation to show preservation of morphology and antigenicity of the transferred tissue.. Prostate cancer patch TMAs were constructed using 20 cores acquired from radical prostatectomy histology slides. The preservation of morphology and antigenicity of these patch TMAs were tested with immunohistochemistry (IHC) in comparison to a traditional TMA.. After IHC staining, 35 of 39 cores (89.7%) on the patch TMA were intact compared with 39 of 40 cores (97.5%) on the traditional TMA. Expression patterns and density of the antigens (34BE12, p63 and AMACR) on the patch TMA were almost identical to the traditional TMA.. Patch TMA represents a viable alternative for tissue-based IHC studies when paraffin blocks are unavailable. This may be a valuable tool for allowing use of archival slide material for IHC and enable a standardized TMA platform to be used when the slides sent for review from other institutions are the only source of tissue available.

Topics: Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Male; Paraffin Embedding; Prostatectomy; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Racemases and Epimerases; Reproducibility of Results; Specimen Handling; Tissue Array Analysis

Immunohistochemical (IHC) staining for ERG is used as a surrogate for TMPRSS2-ERG gene fusion, a specific molecular event seen in ~50% of prostate carcinomas (PCas) and ~20% of high-grade prostatic intraepithelial neoplasia (HGPIN) intermingled with adjacent PCa demonstrating identical gene fusions. We studied 84 "atypical glands suspicious for cancer (ATYP)" cases using multiplex ERG/α-methylacyl-CoA-racemase (AMACR)/high-molecular-weight cytokeratin/p63 IHC to determine how often ERG contributes to resolving an ATYP diagnosis beyond that provided by AMACR and basal markers. Final diagnoses of benign, ATYP, and cancer were rendered after review of morphology and all markers in 3, 30, and 51 cases, respectively. Of 51 cancer diagnoses, 45% and 94% were positive for ERG and AMACR, respectively. Of 30 atypical diagnoses, 10% and 67% were positive for ERG and AMACR, respectively. Of 3 benign diagnoses, none and 83% were positive for ERG and AMACR, respectively. Three ERG-positive atypical cases were classified as "HGPIN with adjacent ATYP." ERG was expressed in adjacent noncancer glands of 20% of PCas, whereas AMACR was expressed in noncancer glands in all diagnostic categories in 40% of cases. Positive ERG staining helped establish the initial ATYP diagnosis to PCa in 28% cases whose diagnoses would otherwise remain ATYP based on AMACR and basal markers. ERG positivity in small atypical glands where HGPIN diagnosis is excluded helps establish a definitive cancer diagnosis in a small proportion of additional ATYP cases. We recommend judicious use of ERG, preferably as a component of multiplex IHC, in evaluation of difficult prostate biopsies.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Middle Aged; Prostate; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Racemases and Epimerases; Trans-Activators; Transcriptional Regulator ERG

Luminal cells are believed to be the cells of origin for human prostate cancer, because the disease is characterized by luminal cell expansion and the absence of basal cells. Yet functional studies addressing the origin of human prostate cancer have not previously been reported because of a lack of relevant in vivo human models. Here we show that basal cells from primary benign human prostate tissue can initiate prostate cancer in immunodeficient mice. The cooperative effects of AKT, ERG, and androgen receptor in basal cells recapitulated the histological and molecular features of human prostate cancer, with loss of basal cells and expansion of luminal cells expressing prostate-specific antigen and alpha-methylacyl-CoA racemase. Our results demonstrate that histological characterization of cancers does not necessarily correlate with the cellular origins of the disease.

Topics: Animals; Biomarkers, Tumor; Cell Separation; Cell Transformation, Neoplastic; Epithelial Cells; Epithelium; Flow Cytometry; Humans; Keratins; Male; Mice; Mice, Inbred NOD; Mice, SCID; Prostate; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Receptors, Androgen; Trans-Activators; Transcriptional Regulator ERG; Transduction, Genetic

Benign prostatic hyperplasia and prostatic adenocarcinoma exhibit prominent zonal predilections. Basal cells from the transitional zone and from the peripheral zone are postulated to have different underlying biological properties. We studied basal cells in both prostatic zones.. Tissue microarrays (TMA) were prepared from 65 whole-mounted prostatectomy specimens with prostatic adenocarcinoma. The transitional zone and peripheral zone were sampled from each prostate. TMA sections were stained with a basal cell cocktail (CK 34betaE12 + p63). The immunostaining pattern and the morphology of basal cells were recorded.. Triangular-shaped basal cells were highlighted by CK 34betaE12 cytoplasmic and p63 nuclear staining. These basal cells had their long axis oriented perpendicular to the basement membrane and their apex toward the lumen interdigited between secretory luminal cells. This morphology was seen in the majority of peripheral zone benign prostatic glands (92.0%) but only a minority of transitional zone benign prostatic glands (18.0%). Basal cells of the transitional zone showed weak or absent CK 34betaE12 staining in 65.9% of glands while maintaining p63. All glands with high-grade prostatic intraepithelial neoplasia (HGPIN) contained the triangular basal cells. In addition, basal cell clusters were identified in 8.7% of peripheral zone glands and 5.2% of HGPIN glands.. Our results indicate that the basal cell morphology and the basal cell immunophenotype have a zonal variation. The finding of a unique morphology of basal cells and the presence of basal cell clusters in the peripheral zone suggests that the peripheral zone might be the stem/progenitor cell-rich area in the human prostates.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Cell Nucleus; Humans; Image Processing, Computer-Assisted; Immunoenzyme Techniques; Keratins; Male; Membrane Proteins; Middle Aged; Neoplastic Stem Cells; Prostate; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Tissue Array Analysis

Typically glands of prostatic adenocarcinoma have a single cell lining, although stratification can be seen in invasive carcinomas with a cribriform architecture, including ductal carcinoma. The presence and diagnostic significance of stratified cells within non-cribriform carcinomatous prostatic glands has not been well addressed. The histomorphological features and immunohistochemical profile of cases of non-cribriform prostatic adenocarcinoma with stratified malignant glandular epithelium were analyzed. These cases were identified from needle biopsy cases from the consultation files of one of the authors and from a review of 150 consecutive in-house needle biopsy cases of prostatic adenocarcinoma. Immunohistochemistry was performed utilizing antibodies reactive against high molecular weight cytokeratin (34betaE12), p63 and alpha-methylacyl-coenzyme-A racemase (AMACR). A total of 8 cases were identified, including 2 from the 150 consecutive in-house cases (1.3%). In 4 cases, the focus with glands having stratified epithelium was the sole carcinomatous component in the biopsy, while such a component represented 5-30% of the invasive carcinoma seen elsewhere in the remaining cases. The main attribute in all these foci was the presence of glandular profiles lined by several layers of epithelial cells with cytological and architectural features resembling flat or tufted high-grade prostatic intraepithelial neoplasia, but lacking basal cells as confirmed by negative 34betaE12 and/or p63 immunostains in all cases. The AMACR staining profile of the stratified foci was variable, with 4 foci showing positivity, and 3 foci being negative, including two cases that displayed AMACR positivity in adjacent non-stratified prostatic adenocarcinoma. Prostatic adenocarcinoma with stratified malignant glandular epithelium can be identified in prostate needle biopsy samples harboring non-cribriform prostatic adenocarcinoma and resembles glands with high-grade prostatic intraepithelial neoplasia. These 'PIN-like' carcinomas can present in pure form. Recognition of this pattern of prostatic adenocarcinoma is necessary to correctly diagnose such cases as invasive carcinoma.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biopsy, Needle; Diagnosis, Differential; Epithelium; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Middle Aged; Neoplasm Invasiveness; Prostate-Specific Antigen; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Racemases and Epimerases; Retrospective Studies

To investigate the value of using an AMACR/34betaE12/p63 cocktail and double-staining for the diagnosis of small focal protatic carcinoma and precarcinomatous lesions.. A total of 130 consecutive cases were examined over a 3-month period, including 105 prostate needle biopsy samples, 6 radical prostatectomy specimens and 19 benign prostatic hyperplasia specimens which were excised transurethra or above pubis. 262 paraffin blocks of all the 1030 ones were stained with hematoxylin and eosin and by immunostains for AMACR, 34betaE12, p63, and an antibody cocktail comprising all the three with double-chromogen reaction. The diagnoses were then made according to the immunostaining, HE staining and clinical information.. In the sections stained by the 3-antibody cocktail, blue-black cytoplasmic staining was observed in the epithelial cells of prostatic carcinoma and high-grade prostatic intraepithelial neoplasia (HGPIN) the basal cells of benign glands were stained red. There were no red basal cells around the blue-black glandular epithelium of carcinoma, but discontinuous or consecutive red basal cells were present around the blue-black glandular epithelium of HGPIN. Prostatic carcinoma was found in 214 paraffin blocks (82%), including 31 small focal carcinoma. HGPIN were observed in 64 paraffin blocks (24%), including focal HGPIN and small gland alveolus HGPIN. AAH was found in one block. No benign glands were simultaneously positive for AMACR and negative for basal cell markers.. Inmmunohistochemistry studies using a 3-antibody cocktail and double staining can improve the detection rate of small focal prostatic carcinoma and HGPIN.

Topics: Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Male; Predictive Value of Tests; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Racemases and Epimerases; Staining and Labeling; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

Despite the high incidence and mortality of prostate cancer (PCa), molecular and genetic events involved in its progression remain poorly understood due to difficulty in establishing premalignant lesions and primary tumors in vitro. The most used cancer cell lines, which have been established primarily from metastatic lesions, do not accurately recapitulate the biological behaviour of primary tumors as compared to primary cultures generated from clinical PCa specimens. However, prostate primary cultures contain a mixture of different cell types which must be characterized completely to obtain reproducible information for studying the biology of single tumors and for evaluating the effectiveness of therapeutical approaches. In this report we show the differential expression of epithelial and prostatic markers in 30 PCa-, 6 high grade prostate intraepithelial neoplasia (PIN)- and 6 BPH-derived primary cell cultures. After organoids attached, outgrowths appeared with cells maintaining close cell-to-cell associations: cell colonies express either cyto-keratin 14 [K14 (20-60%)], or cytokeratin 18 [K18 (10-70%)] with moderately high levels of androgen receptor (AR), prostate-specific antigen (PSA) and kallikrein (hK2). The differences observed for K14 immunostaining was not statistically different between PIN- and BPH-derived cultures, whereas the difference of expression of the same marker resulted highly significant (p<0.001) in the comparison between PIN- and PCa-derived cultures and between BPH- and PCa-derived cultures. In addition, the percentage of positivity for lumenal K18 was statistically lower for BPH cultures respect to the positivity observed for both PIN and PCa-derived cultures (p<0.05 and p<0.001, respectively). A reduced expression of K18+ cells, without modification in K14 expression, was evident in high grade PCa in which we observed also an increment in K5 expression representing an intermediate basal/differentiating epithelial cell marker. The primary cultures derived from prostatic tissues can be an extremely important method to study genetic and molecular changes involved in PCa progression.

Topics: Biomarkers, Tumor; Gene Expression Profiling; Humans; Kallikreins; Keratins; Male; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Receptors, Androgen; Tumor Cells, Cultured

Topics: Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Racemases and Epimerases; Staining and Labeling

Ectopic expression of fibroblast growth factor receptor 1 (FGFR1) tyrosine kinase in epithelial cells is associated with progression of prostate cancer. Ectopic expression by transfection of FGFR1 in premalignant epithelial cells from nonmalignant Dunning tumors accelerated time-dependent progression of epithelial cells to malignancy. This study was designed to test the effect of chronic androgen-dependent ectopic activity of FGFR1 in the normal adult mouse epithelium by gene targeting.. Constitutively active FGFR1 (caFGFR1) was targeted to prostate epithelial cells using the androgen-dependent probasin (PB) promoter. Prostate tissues of three strains were characterized over a period of 2 years by HE staining, immunohistochemical analyses for cytokeratin and alpha-actin, and rate of androgen-induced regeneration after castration.. Relative to wildtype littermates, transgenic mice showed increased overall size, hyperplasia in epithelial, and, to a lesser extent, stromal compartments and nuclear atypia in epithelial cells of the prostate with increasing age. Androgen-induced regeneration after castration was enhanced at day 3 by two-fold in mice expressing ectopic caFGFR1.. The ectopic presence and chronic activation of FGFR1 in mouse prostate epithelial cells induces progressive prostate intraepithelial neoplasia. These results confirm results suggested by the transplantable Dunning tumor and cell culture models that, in contrast to homeostasis-promoting resident FGFR2, chronic ectopic FGFR1 kinase activity in the epithelium disrupts homeostasis between stroma and epithelium. Although insufficient alone, it may cooperate with other oncogenic changes to promote epithelial cells down the path to malignancy.

Topics: Actins; Androgen-Binding Protein; Animals; Epithelial Cells; Female; Immunohistochemistry; Keratins; Male; Mice; Mice, Transgenic; Orchiectomy; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Receptor Protein-Tyrosine Kinases; Receptor, Fibroblast Growth Factor, Type 1; Receptors, Fibroblast Growth Factor; Testosterone

Atypical glands on prostate needle biopsy with a negative 34betaE12 (cytokeratin 903; CK903) immunostain, indicating a lack of a basal cell layer, are typically diagnostic of prostate cancer. However, in certain cases a negative 34betaE12 immunostain in a small focus of atypical glands is still not convincing enough to make the diagnosis of cancer. This study is the first report to evaluate the incidence of prostate cancer on follow-up biopsy in individuals with this diagnosis. A total of 543 men who had prostate core biopsy specimens diagnosed as a small focus of atypical-appearing glands with a negative 34betaE12 immunostain between January 1, 1997 and December 31, 2000 were selected for study. Some 61% of these 543 individuals (n = 332) had undergone at least one follow-up biopsy procedure. Of these, 43% of repeat biopsy cases (n = 142) were diagnostic of prostate cancer. A total of 46 individuals had at least 2 follow-up biopsy procedures, with 48% of these (n = 22) being diagnosed as cancer. The Gleason grades of the detected carcinomas were broken down as follows: Gleason grade 3 + 2 = 5, 6%; grade 3 + 3 = 6, 86%; grade 3 + 4 = 7, 1%; grade 4 + 3 = 7, 4%; and grade 4 + 4 = 8, 3%. The median amount of time to the first follow-up biopsy was 79 days, with 52% of follow-up biopsies performed within 90 days. A negative 34betaE12 immunohistochemical stain in a small focus of atypical glands is not associated with an increased prediction of prostate cancer on follow-up biopsy (43%), compared with previously published data for "small focus of atypical glands" alone (approximately 45%). Because 48% of men with an initial negative biopsy and multiple follow-up biopsy procedures were found to have cancer, more than one repeat biopsy session or more extensive sampling on the first repeat biopsy procedure may be necessary to maximize the identification of cancer. This finding is similar to that found in men with atypical diagnoses in general, without a negative 34betaE12 immunohistochemical stain. Only half of all individuals with a diagnosis of 34betaE12-negative focus of atypical glands underwent repeat biopsy within 3 months. Urologists need to be educated as to the significance of an atypical diagnosis and the need for repeat biopsy. In a small focus of atypical glands on prostate biopsy, negative staining for 34betaE12 should not necessarily lead to a definitive malignant diagnosis in all cases, because almost half of these biopsies on follow-up sampling ar

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy, Needle; Exocrine Glands; Follow-Up Studies; Humans; Keratins; Male; Prostate; Prostate-Specific Antigen; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

Prostate carcinoma and transitional cell carcinoma (TCC) occur in the prostate gland of older dogs and have morphologic similarities when evaluated by light microscopy. The dog is a commonly used animal model for studying human prostate carcinoma; therefore, it is important to accurately differentiate canine prostate carcinomas from TCCs. We investigated whether keratin 7 (K7) and arginine esterase (AE) would aid differentiation of canine prostate carcinoma from TCC. K7 expression was evaluated in normal and neoplastic canine prostate and bladder tissues using immunohistochemistry. The expression of AE messenger ribonucleic acid (mRNA) in normal and neoplastic canine prostate and bladder was detected using northern blots and reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, AE enzyme activity was measured in normal and neoplastic canine prostate and bladder tissues. We found marked similarities in K7 expression in prostate carcinomas and TCCs. AE mRNA was present in high levels in normal prostatic tissue but was reduced in prostate carcinoma by northern blot assay. Nested RT-PCR detected AE mRNA both in TCCs (13 of 15) and in prostate carcinomas (13 of 13). Enzymatic activity of AE was high in normal prostate gland and in some prostate carcinomas, whereas normal bladder and TCCs produced lower levels of AE. In conclusion, K7 and AE cannot be used to differentiate TCC from prostate carcinoma in dogs.

Topics: Animals; Blotting, Northern; Carboxylic Ester Hydrolases; Carcinoma, Transitional Cell; DNA Primers; Dog Diseases; Dogs; Gene Expression; Immunohistochemistry; Keratin-7; Keratins; Male; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Topics: Biomarkers, Tumor; Biopsy, Needle; Humans; Keratins; Male; Oligonucleotide Array Sequence Analysis; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Racemases and Epimerases

To assess the utility of P504S immunohistochemistry in the diagnosis and differential diagnosis of prostatic adenocarcinoma.. Light microscopy and immunohistochemistry examinations (EnVision staining) were performed in 117 cases of prostatic adenocarcinoma, PIN, AAH, ASAP, BPH and normal prostatic tissue to correlate the morphology and protein expression of P504S, 34betaE12, and P63.. Seventy-one of the 78 (91%) cases of prostatic adenocarcinoma stained positive for P504S, with strong cytoplasmic granular staining in most cases, and a weak or intense granular staining along the circumferential luminal and apical cell border membrane in a few cases. Negative P504S immunostaining was observed in 7 of 78 (9%) cases of prostatic adenocarcinoma, all of which were clear cell type prostatic adenocarcinoma. Cases of PIN (9 cases), AAH (6 cases) and ASAP (2 cases) showed various expression levels of P504S. Sixty-five of 68 (96%) cases of normal prostates and BPH were negative for P504S and basal cell hyperplasia cases were also negative.. P504S is a useful marker for microscopic diagnosis of prostatic adenocarcinoma, and immunohistochemistry study using a combination of P504S and 34betaE12/p63 may be of greater benefit in aiding the differential diagnoses.

Topics: Adenocarcinoma; Diagnosis, Differential; DNA-Binding Proteins; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Male; Phosphoproteins; Precancerous Conditions; Prostate; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Racemases and Epimerases; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

There is increasing evidence that neuropeptides, including bombesin, may influence growth, angiogenesis, invasiveness, and metastasis in prostate cancer. One of the molecules tightly involved in the regulation of neuropeptide activity is the integral membrane glycoprotein CD10, or neutral endopeptidase 24.11. The pattern of CD10 expression in hyperplastic and neoplastic conditions of the prostate gland has not been previously described. Immunohistochemical staining for CD10 and high-molecular-weight cytokeratin was performed on 92 cases of paraffin-embedded tissue from needle-core biopsy specimens and prostatectomy specimens. Normal and hyperplastic acini showed strong and distinct membrane (apical and intercellular) and cytoplasmic CD10 expression in basal and secretory cells. In contrast, no intercellular membrane or cytoplasmic staining of secretory cells was seen in any cases of adenocarcinoma with Gleason patterns 2 or 3. A subset of high-Gleason grade adenocarcinoma (patterns 4 and 5) displayed CD10 expression in the secretory cells; those cases shared a distinct morphological pattern. Prostatic intraepithelial neoplasia (PIN) showed consistent absence of intercellular membrane and cytoplasmic CD10 expression in the secretory cells, with preserved expression in basal cells. Interestingly, the basal cells in basal cell hyperplasia lacked CD10 expression, and no expression was noted in the secretory cells in all cases examined. Atrophic acini and those associated with acute and chronic inflammation retained CD10 expression. In conclusion, a consistent differential pattern of CD10 expression was seen in basal cell hyperplasia, PIN, and adenocarcinoma, suggesting a role for CD10 in the pathobiology of the prostate gland.

Topics: Adenocarcinoma; Humans; Keratins; Male; Neprilysin; Prostate; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Seminal Vesicles

We evaluated the sensitivity and specificity of cytokeratin (CK) 5/6 for distinguishing foci of atrophy from prostatic adenocarcinoma with and without previous hormonal adjuvant therapy and observed the intensity and pattern of staining in mimickers of prostatic adenocarcinoma (basal cell hyperplasia, atypical adenomatous hyperplasia, and tangentially cut high-grade prostatic intraepithelial neoplasia [PIN]). We reviewed 146 acinar proliferations in 81 specimens (radical prostatectomy, previously untreated, 41; radical prostatectomy, following androgen-deprivation therapy, 11; transurethral resection, previously untreated, 29). All benign acinar proliferations stained positively for CK5/6, with immunoreactivity restricted to basal cells. Untreated and androgen-deprived prostatic adenocarcinomas were invariably negative. The pattern of staining was continuous in 79% of the atrophy cases (15/19), and all foci stained with CK5/6. Characteristic double-layer staining in basal cell hyperplasia was observed in 93% of cases (13/14), and foci of high-grade PIN had a characteristic "checkerboard" staining with areas of discontinuity. Foci of atypical adenomatous hyperplasia showed continuous staining, including cauterized acini in 53% of cases (8/15), with a fragmented basal cell layer pattern in 47% of cases (7/15). CK5/6 staining of the basal cells in foci of atrophy is sensitive and specific for excluding prostatic adenocarcinoma with and without androgen-deprivation effect.

Topics: Adenocarcinoma; Androgen Antagonists; Atrophy; Diagnosis, Differential; Humans; Keratins; Male; Prostate; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

Rare reports describe high molecular weight cytokeratin (clone 34betaE12) antibody cross-reactivity in scattered prostate carcinoma (PCa) cells, yet most often not in a true basal cell distribution. There are no data specifically describing 34betaE12 reactivity in basal cells in PCa. From August 10, 1995 to May 1, 2000, a total of 3198 consult prostate needle biopsies with PCa and a 34betaE12 immunoperoxidase stain were reviewed at our institution. Thirty-six cases (1.1%), which on hematoxylin and eosin stain were unequivocal cancer, had at least focal 34betaE12 positivity in a basal cell distribution. Twenty-five had original diagnostic slides for review. All cancers were Gleason score 6. The mean number of cancer glands per case was 36.9 (10-108) with an average of 39% of glands (1-100%) showing 34betaE12 reactivity. Twenty-one cases had patchy staining in a basal cell distribution with one other case showing continuous staining. An additional case showed mainly tumor cell reactivity with rare basal cell staining. The final two cases showed a zonal staining pattern with small glands toward one side of the lesion showing basal cells [one with high grade prostatic intraepithelial neoplasia (HGPIN); one without HGPIN]. HGPIN was present in 16 of 25 (64%) cases adjacent to PCa. The mean number of HGPIN glands was 1.36 (1-6). In cases with HGPIN the mean ratio of cancer to HGPIN glands was 6.8 (0.5-13.0). In 12 cases in which the lesion was still present on deeper sectioning, we were able to confirm in nine cases the presence of basal cells using antibodies to p63, another marker for prostatic basal cells. Four of the 25 men underwent radical prostatectomy; all showed Gleason score 6 PCa. Three radical prostatectomies demonstrated 34betaE12 reactivity: two with patchy staining in a basal cell distribution and one with mainly tumor cell staining. Adjacent HGPIN was present in all three radical prostatectomy specimens. Rare lesions with the appearance of PCa show 34betaE12 staining in a basal cell distribution either from retention of basal cells by early invasive cancer or from HGPIN outpouching. The lack of adjacent HGPIN in some cases and the large ratio of small atypical glands to HGPIN glands argue against HGPIN outpouching as the sole explanation. In cases with adjacent HGPIN a comparison of the proximity and number of the small, atypical, infiltrative appearing glands to HGPIN is helpful. The diagnosis of PCa in the face of positive 34betaE12 basal cell

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy, Needle; Fluorescent Antibody Technique, Indirect; Humans; Immunoenzyme Techniques; Keratins; Male; Molecular Weight; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Staining and Labeling

The distinction of basal cell hyperplasia (BCH) from carcinoma or high-grade prostatic intraepithelial neoplasia may be difficult. We reviewed 25 cases of BCH with unusual features and identified four distinct groups: BCH with intracytoplasmic globules (five cases); BCH with calcifications (eight cases), including one with globules; BCH with squamous features (three cases); and cribriform BCH (nine cases), including two cases with globules. A total of five cases contained prominent nucleoli and/or cytologic atypia. Hyaline cytoplasmic globules have not been described in any other prostatic entity and appear diagnostic of BCH. Calcifications observed in BCH were psammomatous, differing from the fine stippled calcifications occasionally seen in areas of comedonecrosis within high-grade prostatic carcinoma. Basal cell hyperplasia with squamous features differed from squamous differentiation in carcinomas (adenosquamous carcinoma) and from benign foci of squamous differentiation seen associated with either prostatic infarcts or with hormonal therapy. Whereas cribriform prostatic intraepithelial neoplasia and cribriform cancer glands represent a single glandular unit with punched out lumina, many of the glands within a focus of cribriform BCH appeared as fused individual BCH glands. The use of cytokeratin 34betaE12 can help in difficult cases. In cribriform BCH high-molecular-weight cytokeratin shows multilayered staining of the basal cells in some of the glands and a continuous layer of immunoreactivity. Cribriform prostatic intraepithelial neoplasia demonstrates an interrupted immunoreactive single cell layer of basal cells. Recognition of the architectural and cytologic features of unusual morphologies of BCH can be used to facilitate its diagnosis and differentiation from prostatic carcinoma and high-grade prostatic intraepithelial neoplasia.

Topics: Carcinoma, Adenosquamous; Diagnosis, Differential; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Male; Prostate; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

Topics: Adenocarcinoma; Biomarkers, Tumor; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Prostate; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

Atypical cribriform lesions on prostate needle biopsy specimens are rare and difficult to diagnose. Of 574 high-grade prostatic intraepithelial neoplasia (PIN) lesions on needle biopsy seen at our institution over 75 months, we identified 23 consult cases in which the differential diagnosis was cribriform high-grade PIN versus infiltrating cribriform carcinoma. Prebiopsy prostate-specific antigen (PSA) averaged 6.5 ng/mL (range, 0.3 to 37.3). A positive digital rectal examination (DRE) was present in 12 of 22 (55%) patients for whom information was available. Ordinary high-grade PIN was present elsewhere in the biopsy specimens in 32% of cases. The following architectural features of cribriform glands were evaluated: number (mean, 5; range, 1 to 21); largest size (mean, 0.5 mm; range, 0.1 to 1 mm); necrosis (14%); detached cribriform fragments (18%); stromal fibrosis (18%); and bilaterality (22%). Cytologically, there was cellular maturation toward the center of the cribriform glands (45%); identifiable basal cells on hematoxylin and eosin sections (36%); marked nuclear atypia (9%); and mitoses (23%). Nucleoli were not visible in 18% of cases, small in 36%, and prominent in 45%. With a mean follow-up of 13.8 months for those without progression (25.9 months' overall follow-up), a repeat biopsy diagnosis of cancer was seen in 10 of 22 men [by report: Gleason score (Gs) 4 (n = 1); Gs 6 (n = 3); Gs 7 (n = 4); Gs 9 (n = 2); three biopsy specimens showed ductal features]. An additional two men developed bone metastases without biopsy. Overall, 12 of 22 (55%) patients had cancer on follow-up (one patient lost to follow-up). Four clinicopathologic findings predicted carcinoma on follow-up: positive DRE (p = 0.02); positive transrectal ultrasound (p = 0.02); bilateral atypical cribriform glands (p = 0.02); and detached cribriform glands (p = 0.04).

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biopsy, Needle; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

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.. 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.. 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.. 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.

Topics: Adenocarcinoma; Biomarkers, Tumor; CD40 Antigens; Humans; Immunohistochemistry; Keratins; Male; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

Routine microscopy provides only a 2-dimensional view of the complex 3-dimensional structure that makes up human tissue. Three-dimensional microscopic image reconstruction has not been described previously for prostate cancer.. To develop a simple method of computerized 3-dimensional image reconstruction and to demonstrate its applicability to the study of prostatic adenocarcinoma.. Serial sections were cut from archival paraffin-embedded prostate specimens, immunostained using antikeratin CAM5.2, and digitally imaged. Computer image-rendering software was used to produce 3-dimensional image reconstructions of prostate cancer of varying Gleason grades, normal prostate, and prostatic intraepithelial neoplasia.. The rendering system proved easy to use and provided good-quality 3-dimensional images of most specimens. Normal prostate glands formed irregular fusiform structures branching off central tubular ducts. Prostatic intraepithelial neoplasia showed external contours similar to those of normal glands, but with a markedly complex internal arrangement of branching lumens. Gleason grade 3 carcinoma was found to consist of a complex array of interconnecting tubules rather than the apparently separate glands seen in 2 dimensions on routine light microscopy. Gleason grade 4 carcinoma demonstrated a characteristic form of glandular fusion that was readily visualized by optically sectioning and rotating the reconstructed images.. Computerized 3-dimensional microscopic imaging holds great promise as an investigational tool. By revealing the structural relationships of the various Gleason grades of prostate cancer, this method could be used to refine diagnostic and grading criteria for this common tumor.

Topics: Adenocarcinoma; Biomarkers; Humans; Imaging, Three-Dimensional; Immunohistochemistry; Keratins; Male; Microtomy; Paraffin Embedding; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

We performed immunohistochemical studies of the prostatic epithelium using three different anti-cytokeratin monoclonal antibodies (35 beta-H11, RCK108, and 34 beta-E12), and also investigated the immunoreactivity of various prostatic lesions with basal cell specific anti-cytokeratin antibody (34 beta-E12).. One hundred and thirty one prostatic specimens were obtained at surgery or biopsy. H-E stained sections were available for review in all cases. They were classified according to histopathology; benign prostatic hyperplasia (BPH), prostatic cancer (PCA), atrophic acini, atypical adenomatous hyperplasia (AAH), and prostatic intraepithelial neoplasia (PIN). ABC or LSAB method was utilized for immunohistochemical staining with 3 anti-cytokeratin monoclonal antibodies.. 35 beta-H11 was mainly stained in the luminal cells and RCK108 was stained both in the luminal and the basal cells in BPH. 35 beta-H11 showed highly positive staining in the prostatic cancer regardless of degree of differentiation. RCK108 tended to be less stained in the prostatic cancer cells with lower grades of tumor differentiation compared to those with higher grades. 34 beta-E12 was stained only in the basal cells, but neither in the normal luminal cells nor the cancer cells. Using 34 beta-E 12, basal cells were positively stained in most of the cases with BPH, while not in PCA. Atrophic acini and AAH was stained with 34 beta-E12 as positively as BPH. Basal cells were discontinuously or negatively stained in many cases with high-grade PIN.. The luminal cells in BPH were highly positively stained using 35 beta-H11 or RCK108. RCK108 tended to be less stained in the prostatic cancer cells with lower grades of tumor differentiation. Positive staining of 34 beta-E12 strongly suggested a benign lesion, therefore immunohistochemistry using this antibody would be useful as an aid for pathological diagnosis.

Topics: Antibodies, Monoclonal; Epithelium; Humans; Immunohistochemistry; Keratins; Male; Prostate; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

A 60-year-old man underwent radical prostatectomy for biopsy-proved adenocarcinoma of the prostate. Histologic examination of the entirely embedded prostatectomy specimen revealed extensive ordinary adenocarcinoma, Gleason's grade 3 + 3 = 6, involving both sides of the gland, and extending into extraprostatic soft tissue at the left base. Adjacent to the carcinoma, and separately, extensive high-grade prostatic intraepithelial neoplasia (PIN) was identified, much of which showed bland nuclei and abundant xanthomatous cytoplasm, identical morphologically to that seen in foamy gland prostate carcinoma. However, unlike foamy gland carcinoma, the foamy glands in the current patient were large, showed papillary infolding, and were associated with a discontinuous layer of basal cells, demonstrated by immunostaining for high-molecular weight cytokeratin. No invasive foamy gland carcinoma was identified in the prostatectomy specimen. Immunostains for Ki-67 showed an increased proliferation rate in foamy high-grade PIN glands when compared with adjacent benign glands. Review of additional outside biopsy material revealed foamy gland high-grade PIN on four of seven needle cores, two of which showed no carcinoma. This patient demonstrates a new subtype of high-grade PIN that is difficult to recognize on needle biopsy. It is important to distinguish foamy gland high-grade PIN from its infiltrating counterpart, and it is critical to recognize because of the association of high-grade PIN with prostate carcinoma.

Topics: Adenocarcinoma; Biopsy, Needle; Humans; Keratins; Male; Middle Aged; Neoplasms, Multiple Primary; Prostate; Prostatectomy; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Staining and Labeling

In select cases of prostatic carcinoma, antikeratin 34betaE12 immunohistochemical analysis is diagnostically useful for specific labeling of basal cells. This antibody, however, is prone to variability in staining, and the optimal conditions were not, to our knowledge, previously defined. We combined steam heat with EDTA buffer (steam-EDTA) and protease digestion (steam-EDTA + protease) to optimize epitope retrieval of antikeratin 34betaE12 in 42 cases of prostatic cancer. Results were judged by the percentage of cells staining and by staining intensity. In benign epithelium, steam-EDTA + protease significantly increased the percentage of immunoreactive cells (from 74 to 93%) and the intensity of staining (from 2.1 to 3.0 on a scale of 0-3+) by comparison with protease alone (all P<.001). In high-grade prostatic intraepithelial neoplasia, the percentage of cells staining increased from 55 to 73% and intensity increased from 1.7 to 2.8 (both P<.001). Steam-EDTA + protease also minimized variability in results between cases, with essentially no background stromal staining. Cancer was negative in all of our cases by both methods. We conclude that steam-EDTA + protease significantly enhances basal cell immunoreactivity compared with protease treatment alone in noncancerous prostatic epithelium. This helps to prevent misinterpretation of histologic mimics of cancer, such as atrophic acini and high-grade prostatic intraepithelial neoplasia, that result from false-negative staining.

Topics: Antibodies, Monoclonal; Buffers; Edetic Acid; Hot Temperature; Humans; Immunohistochemistry; Keratins; Male; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Staining and Labeling; Steam

To determine the rate of diagnostic uncertainty in rendering diagnoses on prostate needle biopsies and to examine pathology practice variables that influence that rate.. Anatomic pathology departments participating in the College of American Pathologists Q-Probes laboratory quality improvement program retrospectively reviewed their last 50 consecutive prostate needle biopsy diagnoses. For each diagnosis, participants provided information concerning patients' prostate-specific antigen levels; number, locations, and laterality of biopsy specimens; number of tissue levels examined; performance of high-molecular-weight cytokeratin immunoperoxidase staining; and acquisition of consultations from general pathologists or experts in prostate pathology. Characteristics of pathology practices included yearly surgical and prostate needle biopsy caseloads, number of pathologists rendering biopsy diagnoses, use of standard descriptive checklists, access to patients' prostate-specific antigen and digital rectal examination results, percentages of prostate needle biopsies routinely submitted for internal consultations, and presence of departmental experts in prostate pathology.. Three hundred thirty-two public and private institutions located in the United States (n = 318), Canada (n = 6), Australia (n = 5), United Kingdom (n = 2), and Guam (n = 1).. The rate of diagnostic uncertainty in prostate needle biopsy diagnoses.. Participants submitted diagnoses on a total of 15 753 prostate needle biopsy cases, of which 33.4% were adenocarcinoma; 55.5% were benign; 3.9% were carcinoma in situ, prostatic intraepithelial neoplasia, or both; and 7.1% were diagnostically uncertain. The median rate of diagnostic uncertainty was 6%, ranging from 0 at the 10th percentile to 14% at the 90th percentile of all participating laboratories. Performing high-molecular-weight cytokeratin immunoperoxidase staining resolved diagnostic uncertainty in 68% of cases in which it was performed, and obtaining intradepartmental and extradepartmental consultations resolved diagnostic uncertainty in 70% to 87% of cases for which they were obtained. Knowledge of patients' prostate-specific antigen results and examining multiple biopsy cores had marginal effects on the rate of uncertainty. Thoroughness of prostate gland sampling and examination of multiple tissue block levels were not associated with the aggregate rate of diagnostic uncertainty. We found no particular pathology departmental practices or institutional demographic characteristics associated with institutional rates of diagnostic uncertainty.. Use of high-molecular-weight cytokeratin immunoperoxidase staining and obtaining intradepartmental and extradepartmental consultations may be effective in reducing diagnostic uncertainty in prostate biopsies.

Topics: Adenocarcinoma; Biopsy, Needle; Carcinoma in Situ; Humans; Immunoenzyme Techniques; Keratins; Male; Palpation; Pathology; Prostate-Specific Antigen; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Quality Control; Rectum; Sensitivity and Specificity

Expression of KAI1, a tumor metastasis suppressor gene, was studied with different fixatives in frozen and paraffin-embedded sections of human and rat prostate carcinoma cell lines and human prostate lesions by immunohistochemistry. Immunoreactivity of the membrane antigen in cell lines was associated with known expression levels in these lines and the fixative used. Formalin and paraformaldehyde helped maintain the immunoreactivity of cells. In human prostate, frozen sections revealed diffuse reactivity of the antigen in normal and neoplastic tissues while paraffin-embedded tissues usually showed focal reactivity, although more than 50% of cases with normal epithelium and adenocarcinomas were reactive. In some cases, pretreatment with trypsin enhanced immunoreactivity. Benign prostatic hyperplasia (BPH) showed the most intense diffuse immunoreactivity, which suggested enhanced expression. Prostatic intraepithelial neoplasia (PIN) also often expressed high levels of KAI1. Three of five metastases were reactive but two primaries and their metastases were not. Lymphocytes in primary carcinomas and lymphocytes and germinal center cells in lymph nodes were immunoreactive, while adjacent primary or metastatic prostate adenocarcinoma epithelium was not immunoreactive. Although paraffin-embedded human tissues were not optimal for determining levels of expression of KAI1, they did show immunoreactivity that could have prognostic value and showed the specific cytoplasmic localization of the protein in cells.

Topics: Adenocarcinoma; Animals; Antigens, CD; Frozen Sections; Humans; Immunohistochemistry; Kangai-1 Protein; Keratins; Male; Membrane Glycoproteins; Paraffin Embedding; Prostate; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Proto-Oncogene Proteins; Rats; Tumor Cells, Cultured

A wide variety of architectural patterns of adenocarcinoma may be seen in the prostate. We have recently encountered a hitherto-undescribed pattern of growth characterized by intraluminal ball-like clusters of cancer cells reminiscent of renal glomeruli, which we refer to as prostatic adenocarcinoma with glomeruloid features. To define the architectural features, frequency, and distribution of prostatic adenocarcinoma with glomeruloid features, we reviewed 202 totally embedded radical prostatectomy specimens obtained between October 1992 and April 1994 from the files of the Mayo Clinic. This series was supplemented by 100 consecutive needle biopsies with prostatic cancer from January to February 1996. Prostatic adenocarcinoma with glomeruloid features was characterized by round to oval epithelial tufts growing within malignant acini, often supported by a fibrovascular core. The epithelial cells were sometimes arranged in semicircular concentric rows separated by clefted spaces. In the radical prostatectomy specimens, nine cases (4.5%) had glomeruloid features. The glomeruloid pattern constituted 5% to 20% of each cancer (mean, 8.33%) and was usually located at the apex or in the peripheral zone of the prostate. Seven cases were associated with a high Gleason score (7 or 8), one with a score of 6, and one with a score of 5. All cases were associated with high-grade prostatic intraepithelial neoplasia and extensive perineural invasion. Pathological stages included T2c (three cases), T3b (four cases), and T3c (two cases); one of the T3b cases had lymph node metastases (N1). Three (3%) of 100 consecutive routine needle biopsy specimens with cancer showed glomeruloid features, and this pattern constituted 5% to 10% of each cancer (mean, 6.7%). The Gleason score was 6 for two cases and 8 for one case. Two cases were associated with high-grade prostatic intraepithelial neoplasia, and one case had perineural invasion. Glomeruloid features were not observed in any benign or premalignant lesions, including hyperplasia and intraepithelial neoplasia. Glomeruloid structures in the prostate represent an uncommon but distinctive pattern of growth that is specific for malignancy. Glomeruloid features may be a useful diagnostic clue for malignancy, particularly in some challenging needle biopsy specimens. This pattern of growth is usually seen in high-grade adenocarcinoma, often with extraprostatic extension. Further investigations are required to determine its independen

Topics: Adenocarcinoma; Aged; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucins; Neoplasm Staging; Prognosis; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

The identification of basal cells by the basal-cell-specific anti-cytokeratin antibody 34 beta E12 has been shown to be useful in the diagnosis of prostate carcinoma. To determine the usefulness of 34 beta E12 in prostate biopsies we examined formalin-fixed needle biopsy specimens. In a 17-month period 796 prostate needle biopsies obtained from 293 patients were evaluated on hematoxylin and eosin stains; all 796 biopsy specimens were immunostained as well. Immunostaining with 34 beta E12 reduced the rate of equivocal cases from 5.1% to 1.0% and additionally offered a means of quality assurance by confirming the diagnoses of 61 prostate carcinomas made on the basis of biopsy specimens.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Antibody Specificity; Basement Membrane; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Precancerous Conditions; Prostate; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Sensitivity and Specificity

The expression of cytokeratin (CK) mRNA for CK5, -8, -14, -16, and -19 was investigated in normal prostate, prostatic intraepithelial neoplasia (PIN) lesions, and invasive carcinoma using in situ hybridization. Protein localization was carried out in adjacent sections using immunohistochemistry and correlated with mRNA expression. Snap-frozen human prostate samples including 22 examples of normal glands, 20 cases of PIN lesions, and 12 cases of invasive carcinoma were examined. CK5 and -14 mRNA and protein were prominently expressed only in the basal cells of normal glands and PIN lesions. CK14 mRNA was absent in the luminal cells of the most of the PIN lesions but was seen at a low level in some PIN lesions. CK14 protein was not detected in any PIN lesion, suggesting that, if the cell that makes up the PIN lesions is derived from a basal cell, CK14 translation is depressed although a low level of CK14 mRNA may persist. CK8 mRNA and protein were constitutively expressed in all epithelia of normal and abnormal prostate tissues. CK19 mRNA and protein were persistently expressed in both basal and luminal cells of the tubular portion of normal glands as well as PIN lesions, but were expressed heterogeneously in both basal and luminal cells of normal alveoli. CK16 mRNA was expressed in a similar pattern as CK19, but CK16 protein was not detected either in normal or in abnormal prostate tissues. In conclusion, the expression of CK19 in PIN lesions is similar to its tubular expression and would support an origin of PIN lesions from this structure rather than the alveolar portion of the glands. The similar cytokeratin expression between PIN lesions and invasive carcinoma further supports the concept that PIN is a precursor lesion of invasive carcinoma.

Topics: Carcinoma; Humans; In Situ Hybridization; Keratins; Male; Neoplasm Invasiveness; Prostate; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Reference Values; RNA, Messenger

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.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Chromogranins; Humans; Keratins; Male; Microscopy, Electron; Middle Aged; Neoplasms; Precancerous Conditions; Prostate-Specific Antigen; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms

Insulin-like growth factor (IGF)-binding proteins (IGFBPs) modulate the activity of IGFs. In vitro human prostate epithelial cells secrete IGFBP-2 and -3. In vivo IGFBP-2 is increased, and IGFBP-3 is decreased in the serum of patients with prostate cancer. Immunohistochemistry and in situ hybridization were performed to compare the expression of IGFBP-2 and -3 in vivo in prostate tissue containing benign epithelium, high grade prostate intraepithelial neoplasia (PIN), and adenocarcinoma. Immunoreactivity and messenger ribonucleic acid (mRNA) hybridization signals for IGFBP-2 and -3 were localized to epithelial cells. IGFBP-2 immunostaining intensity was significantly increased in PIN regions compared to that in normal epithelium and was further increased in malignant cells. IGFBP-2 mRNA was also significantly increased in PIN and cancer cells. IGFBP-3 immunoreactivity was significantly increased in PIN regions compared to normal epithelium; however, IGFBP-3 protein was significantly decreased in malignant cells. IGFBP-3 mRNA remained virtually unchanged in benign epithelium, PIN, and adenocarcinoma cells. These results demonstrate that increased IGFBP-2 protein in PIN and malignant cells is probably due to increased mRNA expression. However, levels of IGFBP-3 protein may be due to pre- and/or posttranslational mechanisms, including proteolysis. The changes in IGFBP-2 and -3 protein levels in prostatic tissue are in agreement with serum changes reported in patients with prostate cancer.

Topics: Adenocarcinoma; Aged; Epithelium; Humans; Immunohistochemistry; In Situ Hybridization; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Keratins; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; RNA, Messenger

In order to understand the characteristics of proliferative and malignant prostate lesions and to improve the differential diagnosis, immunohistochemical methods using high molecular weight cytokeratin monoclonal antibody 34BE12 to stain the basal cells and to differentiate prostate cancer from hyperplasia in 82 prostate biopsies and specimens, which included 21 adenocarcinoma, 30 intraepithelial neoplasia, 5 atypical adenomatous hyperplasia, 8 basal cell hyperplasia, 11 atrophy of prostate, 4 postatrophic hyperplasia and 3 cribriform hyperplasia. It was demonstrated that the basal cell layer was lost in all prostate adenocarcinomas, but existed in most of the proliferative lesions except for atypical adenomatous hyperplasia and grade 3 intra-epithelial neoplasia in which the basal layer was disrupted in some cases. The study showed that the 34BE12 antibody was useful in the differential diagnosis of prostate adenocarcinoma.

Topics: Adenocarcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Molecular Weight; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms