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PubMed2003

High-grade prostatic intraepithelial neoplasia and prostate cancer risk reduction.

High-grade prostatic intraepithelial neoplasia (PIN) is the earliest accepted stage in carcinogenesis, possessing most of the phenotypic and biochemical changes in cancer without invasion of the basal membrane of the acini. The support for high-grade PIN as the main premalignant lesion of prostate cancer is based on several lines of evidence derived from prostate cancer animal models, epidemiological, morphological, genetic, and molecular studies. The incidence of high-grade PIN averages 9% (range 4-16%) in prostate biopsies, representing 115,000 new cases of high-grade PIN diagnosed each year in the United States. Performing saturation prostate biopsies to rule out any coexistent prostate cancer followed by every 3-6 month serial repeated prostate biopsies is currently the only way in which to manage patients found to have high-grade PIN. Medical therapy for high-grade PIN may easily become the mainstay treatment for high-grade PIN. Treatment of high-grade PIN appears to be of clinical benefit notwithstanding the potential for prostate cancer risk reduction. These clinical benefits would reduce morbidity, enhance quality of life, delay surgery or radiation, and increase the interval for surveillance requiring invasive procedures.

Animals↗

PubMed1999

Prostatic intraepithelial neoplasia in prostate specimens: frequency, significance and relationship to the sampling of the specimen (a retrospective study of 121 cases).

OBJECTIVES: To determine the frequency of PIN (prostatic intraepithelial neoplasia) in prostate specimens and the relationship of PIN with PCA (prostatic carcinoma) and amount of sampling of the specimen. MATERIALS AND METHODS: All the haematoxylin-eosin stained slides of 121 cases diagnosed between 1990 and 1995 were re-examined retrospectively. The amount of sampling of prostate specimens was also re-examined. RESULTS: PIN was observed in 47.9% of all prostate specimens. The frequency of incidental PIN was 71.4% in cystoprostatectomy specimens. PIN was present in 58.3% of the cases with PCA. We observed foci of high-grade PIN adjacent to sites of invasive carcinoma in 100.0% of prostatectomy specimens with PCA. PIN was high-grade in 100.0% of the carcinomatous prostates with PIN. It was multifocal in 53.4% of 58 cases with PIN. Incidental PCA was identified in 14.3% of cytoprostatectomies for bladder cancer. The average number of paraffin blocks of prostatic tissue was 4.1 (+/-2.6) in cases with PIN and 3.2 (+/-1.4) in cases without PIN. CONCLUSION: In prostate specimens, the determination of PIN is very important since it is the most likely precursor of PCA. The probability of detecting PIN and PCA in a prostate specimen is directly related to the amount of sampling.

Adult↗

PubMed2001

Prospective study of correlations between biopsy-detected high grade prostatic intraepithelial neoplasia, serum prostate specific antigen concentration, and race.

BACKGROUND: High grade prostatic intraepithelial neoplasia (HGPIN), a premalignant lesion of the prostate gland, is more common in black men than in white men. The influence of HGPIN on the serum prostate specific antigen (PSA) concentration is controversial, and correlations between HGPIN and PSA in black men and white men have not been investigated. METHODS: Between January 1992 and December 1998, 411 black men and 639 white men with suspected prostate carcinoma underwent an initial benign prostate biopsy at a single medical center. The presence or absence of HGPIN in the biopsy specimens was determined by one uropathologist. RESULTS: HGPIN was identified in 8.9% of the specimens. When stratified by PSA concentration (< 4.0 ng/mL, 4.0-9.9 ng/mL, and > or = 10.0 ng/mL), HGPIN was associated with an increased PSA concentration only among men with PSA concentrations < 4.0 ng/mL (P = 0.01). The prevalence of HGPIN in the black and white patients was 13.4% and 5.9%, respectively (P < 0.0001), and was significantly greater in black men than in white men with PSA concentrations < 4.0 ng/mL (P = 0.002). Among the patients with PSA concentrations < 4.0 ng/mL, black race was an independent predictor of an increased PSA concentration when adjusted for patient age, prostate volume, and the presence or absence of HGPIN (P = 0.03). CONCLUSIONS: HGPIN is more common in black men than in white men and may produce an increase in the PSA concentration. However, racial differences in the prevalence of HGPIN may not contribute to racial differences in PSA concentrations among men with no clinical or histologic evidence of carcinoma.

Adult↗

PubMed2002

Fas and Fas ligand expression is elevated in prostatic intraepithelial neoplasia and prostatic adenocarcinoma.

BACKGROUND: Fas is a Type I membrane receptor of the tumor necrosis factor/nerve growth factor family. On binding to Fas ligand, a Type II transmembrane protein, the Fas/Fas ligand complex, induces apoptosis in target cells. Dysregulation of Fas and Fas ligand expression has been found in some malignant neoplasms. METHODS: Using immunohistochemical analysis, the authors studied the expression of Fas and Fas ligand in prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia (PIN), and adjacent benign prostate tissue from 95 radical prostatectomy specimens. RESULTS: The percentage of cells that stained positively with Fas in benign prostate tissue (mean, 2%) was statistically significantly lower compared with that in prostatic intraepithelial neoplasia (mean, 13%; P = 0.0014) and prostatic adenocarcinoma (mean, 31%; P = 0.0001). The staining intensity of Fas was significantly less in benign prostate tissue compared with the staining intensity in PIN and prostatic adenocarcinoma. The percentage of cells that stained positively with Fas ligand in benign prostate tissue (mean, 13%) was statistically significantly lower compared with that in PIN (mean, 47%; P = 0.0001) and in prostatic adenocarcinoma (mean, 53%; P = 0.0001). The staining intensity of Fas ligand was significantly less in benign prostate tissue compared with that in PIN and prostatic adenocarcinoma. CONCLUSIONS: Data from the current study indicate that Fas/Fas ligand is elevated in prostatic malignancy, suggesting that Fas-mediated apoptosis may be a potential target for therapeutic intervention.

Adenocarcinoma↗

PubMed1995

High grade prostatic intraepithelial neoplasia in prostates removed following irradiation failure in the treatment of prostatic adenocarcinoma.

Prostatic Intraepithelial Neoplasia (PIN) is widely considered to be a precursor lesion for adenocarcinoma of the prostate. No information is available, however, on the sensitivity of PIN to irradiation or the distribution of residual PIN after radiotherapy. We studied a series of forty-six totally embedded, whole mounted, serially sectioned prostates removed by salvage radical retropubic prostatectomy following irradiation failure in which no hormonal therapy/ablation had been undertaken. The mean age of patients was 65 (56-74) years, the mean dose of radiotherapy was 7,266 (6,000-9,000) cGy (15 external beam, 27 external beam plus iridium or gold seed, 3 iodine, and 1 unknown) and the mean interval for irradiation therapy to prostatectomy was 60 (16-145) months. Thirty-two (70%) of the patients had high grade PIN within the prostatectomy specimen. The pattern of PIN was recorded as described by Bostwick and co workers. The frequency of the different patterns per positive case paralleled in rank those in Bostwick's series of non-irradiated prostates, with the most common to least common per patient being: tufting (78.1%), micropapillary (59.3%), cribriform (34.4%) and flat (15.6%). However, the mean number of foci of PIN per prostate was less than in Bostwick's series (7.1 foci vs. 17 foci). There was no statistically significant difference between groups with or without high grade PIN with regard to various clinical factors (last preoperative serum PSA, age, dose of radiotherapy, interval from irradiation therapy to prostatectomy, Kaplan-Meier survival), or pathologic factors (presence of confined tumor, extracapsular extension, positive surgical margins, seminal vesicle invasion, or positive lymph nodes on permanent sections). We conclude that high grade PIN is common in the prostates of patients who have failed irradiation therapy and that, theoretically, not all recurrent tumors derive from regrowth of the initial, incompletely eradicated tumor. However, because there was no significant difference between the two groups with regard to the clinical and pathologic parameters listed, we consider it likely that most recurrent tumors derive from the initial incompletely eradicated tumor.

Adenocarcinoma↗

PubMed2006

A comparison of p21 and p27 immunoexpression in benign glands, prostatic intraepithelial neoplasia and prostate adenocarcinoma.

OBJECTIVE: To assess the immunoexpression of p21 and p27 proteins in consecutive areas of benign glands, prostatic intraepithelial neoplasia (PIN) and prostate adenocarcinoma. PATIENTS AND METHODS: Tissue from 91 patients who had a radical prostatectomy was assessed by immunohistochemistry to evaluate the expression of p21 and p27 in adjacent areas of benign glands, PIN and prostate adenocarcinoma. The results were correlated with various clinicopathological variables, e.g. age, total prostate-specific antigen level, tumour stage, Gleason score, surgical margin involvement, extraprostatic extension, seminal vesicle invasion, and perineural invasion. RESULTS: The p27 score in PIN was lower than that in benign glands (P = 0.04) but there was no significant difference between the scores for PIN and tumour. By contrast, p21 expression was almost undetectable in benign glands, although there was substantially more in PIN and tumour (P < 0.01). Some patients had no expression of p21 in tumour tissue, and had lower p21 scores in benign glands and PIN areas (P < 0.05). Interestingly, these patients had a lower frequency of negative prognostic variables. The tumour p21 score was higher in patients with extraprostatic extension (P = 0.045) and tumour p27 expression was inversely correlated with seminal vesicle invasion (P = 0.028). Tumour and PIN p27 expression appeared to decrease with advancing age (P = 0.008 and 0.012, respectively). CONCLUSION: Higher p21 and lower p27 expression is correlated with adverse prognostic factors. The decline in p27 with advancing age in tumour and PIN areas may be a possible explanation of the greater frequency of prostate adenocarcinoma in older men. A p21-negative tumour subgroup with a lower frequency of adverse prognostic factors was identified, which needs to be further explored.

Adenocarcinoma↗

PubMedDate not supplied

Significance of high-grade prostatic intraepithelial neoplasia on prostate biopsy.

The early diagnosis of prostate cancer has been facilitated by the development of serum prostate-specific antigen (PSA) testing and evolution in transrectal ultrasound-guided biopsy of the prostate. Over a decade has passed since the initial recommendations for systematic sextant sampling of the prostate to increase the accuracy of cancer detection. Subsequently, variations in the number and location of biopsies have been proposed to maximize prostate cancer detection and obtain more complete information regarding tumor grade, tumor volume, and local stage. Although current biopsy strategies provide a wide sampling of the prostate gland, biopsy histology may not be conclusive for either the presence or absence of adenocarcinoma. High-grade prostatic intraepithelial neoplasia (HGPIN) is found in a significant fraction of patients undergoing transrectal prostate biopsies. In this article, we discuss the significance of high-grade prostatic intraepithelial neoplasia and other abnormal histology findings and current evidence addressing the presence of cancer and need for additional prostate biopsies.

Adenocarcinoma↗

PubMed2002

Dysregulation of annexin I protein expression in high-grade prostatic intraepithelial neoplasia and prostate cancer.

PURPOSE: To determine expression levels of annexin I (lipocortin I) in patient-matched benign prostatic epithelium (BPE), high-grade prostatic intraepithelial neoplasia (HGPIN), and prostate cancer (CaP). EXPERIMETNAL DESIGN: Annexin I protein expression was examined with a standard immunohistochemical protocol in 69 radical prostatectomy specimens, 45 of which also contained HGPIN. Immunostained sections were scored visually by a genitourinary pathologist and mean optical density was measured with digital image analysis. Real-time fluorescence quantitative PCR was used to measure expression levels of annexin I mRNA in patient-matched CaP and BPE from 14 snap-frozen, radical prostatectomy specimens. RESULTS: Annexin I protein expression was reduced in 91% (41/45) of HGPIN lesions and 94% (65/69) of invasive CaP compared with BPE in the same histological section when assessed visually. Mean absorbance was reduced significantly (P < 0.05) in 97.7% (44/45) of HGPIN lesions and 98.5% (68/69) of CaP glands compared with BPE. In 79% of cases (11/14; P < 0.05), mRNA expression was reduced in CaP as compared with patient-matched BPE. Annexin I mRNA and protein expression levels did not correlate with Gleason grade, pathological stage, or race. CONCLUSIONS: Down-regulation of annexin I protein expression is a common finding in HGPIN and CaP, suggesting that annexin I dysregulation may be an important early event in CaP initiation. Because mRNA levels are reduced in a high proportion of cases, one likely mechanism for annexin I dysregulation occurs at the level of gene transcription. Results of these studies support a valuable role for a molecular profiling approach to CaP research.

Annexin A1↗

PubMed2001

Inducible nitric oxide synthase expression in benign prostatic hyperplasia, low- and high-grade prostatic intraepithelial neoplasia and prostatic carcinoma.

OBJECTIVE: To elucidate the incidence of inducible nitric oxide synthase (iNOS) expression in benign prostatic hyperplasia (BPH), low- and high-grade prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma lesions, and to explore the role of iNOS in prostate tumorigenesis. MATERIALS AND METHODS: Immunoreactivity for iNOS was examined in 20 samples each of BPH, high-grade PIN, low-grade PIN and prostatic carcinoma. RESULTS: Positive iNOS immunostaining was detected in all samples from all patients; iNOS was detected in both basal epithelial cells and secretory cells of the glandular epithelium. High-grade PIN and prostatic carcinoma samples had more intense iNOS immunostaining than low-grade PIN and BPH samples. In all samples, smooth muscle cells showed weak or moderate iNOS immunoreactivity and endothelial cells showed moderate immunostaining. CONCLUSIONS: Nitric oxide generated by iNOS may be involved in prostate tumorigenesis and further studies with immunohistochemical and molecular biology are needed to determine the exact role of iNOS in the pathogenesis of prostatic carcinoma.

Adenocarcinoma↗

PubMed2003

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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Carcinoma↗

PubMed2000

Nuclear changes in the normal-looking columnar epithelium adjacent to and distant from prostatic intraepithelial neoplasia and prostate cancer. Morphometric analysis in whole-mount sections.

Subtle morphological changes and molecular alterations have been reported in normal-appearing tissue in prostates with high-grade prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa). The severity and the distribution of these changes and alterations within the prostate gland have not been addressed in previous publications. The aim of this study was to investigate morphometrically the nuclear changes of the normal-looking columnar epithelium adjacent to and distant from high-grade PIN and PCa. Karyometry was performed on the whole-mount histological sections of three radical prostatectomy (RP) specimens. Two concentrical lines, one corresponding to the outer surface (or capsule) of the prostate and the other corresponding to one centimeter towards the center, were drawn with a black pen on each whole-mount section. The part of the prostate tissue between these two boundaries was then divided into twelve equal sectors or regions. The part within the inner line was divided into two regions. The analysis was also performed on the slides of the apex and base of the prostate. One prostate contained normal-looking epithelium only (case no. 1). Another contained both high-grade PIN and PCa, the former occupying larger areas than the latter (case no. 2). Both high-grade PIN and PCa were present in the third sample, in which PCa was more widely distributed than PIN (case no. 3). The lesion measured in each region was always the most severe, e.g., either high-grade PIN or PCa. When neither were identifiable, then the normal-looking columnar epithelium was analyzed. For each sector, the mean and standard deviation of the nuclear area, maximum nuclear diameter, nuclear roundness factor, and nucleolar area were calculated. In normal-looking columnar epithelium, the mean of the mean nuclear area of the sectors of case no. 1 was 35.19 microm2 (SD 4.14). The mean nuclear areas in cases no. 2 and no. 3 were 37.94 microm2 (SD 4.65) and 37.31 microm2 (SD 4.36), respectively. The mean of the mean nuclear area of the sectors with high-grade PIN of case no. 2 was 49.85 microm2 (SD 8.44), whereas it was 54.26 microm2 (SD 2.91) in case no. 3. The mean of the nuclear area values obtained in the sectors of cases no. 2 and no. 3 with PCa was 56.74 microm2 (SD 6.56) and 61.17 microm2 (SD 8.13), respectively. When considering the normal-looking tissue of the second and third case, 79% and 90%, respectively, of the regions showed nuclear area values greater than 34.94 microm2 (e.g., the 50th percentile of the mean nuclear area values of the regions of the first case). Sectors with normal-looking epithelium, whose nuclear area was above this threshold, were both adjacent to and at a distance of more than 1 cm from those with PIN or PCa. The other nuclear features showed a similar trend of value changes. This study demonstrates that the normal-looking ducts and acini from prostate harboring preneoplastic and neoplastic lesions show morphological nuclear abnormalities that are not seen by the human eyes but that can be detected with image analysis. Such changes may be of diagnostic importance, especially in cases where clinical suspicion for cancer prevails after a negative biopsy.

Aged↗

PubMed1998

Altered expression of RET proto-oncogene product in prostatic intraepithelial neoplasia and prostate cancer.

BACKGROUND: The RET proto-oncogene encodes a protein that belongs to the tyrosine kinase growth factor receptor family. Germline point mutations in RET are found in individuals with multiple endocrine neoplasia (MEN) syndromes, and gene rearrangements have been reported in papillary thyroid cancers. We recently identified transcripts of the RET proto-oncogene in human prostate cancer xenografts and prostate cancer cell lines by means of reverse transcription-polymerase chain reaction analyses. The purpose of this study was to investigate Ret protein expression in human prostate tissue. METHODS: Ret protein expression was evaluated immunohistochemically in formalin-fixed, paraffin-embedded whole-prostate sections. The prostate specimens were obtained from 30 patients with prostate cancer after radical prostatectomies. Ret protein expression was compared in tumor foci and benign prostatic tissue. Medullary thyroid carcinoma tissue associated with an MEN syndrome and papillary thyroid cancer tissue served as positive controls. RESULTS: Ret appeared to be overexpressed in high-grade (histopathologically advanced) prostatic intraepithelial neoplasia (PIN) and prostate cancer when compared with its expression level in benign prostatic secretory epithelium. In addition, there was an apparent increase in Ret protein expression with decreased cellular differentiation, i.e., increasing Gleason pattern. CONCLUSION: Expression of the RET proto-oncogene in benign prostatic epithelium, high-grade PIN, and histopathologically advanced prostate cancer suggests that RET may play a role in the growth of both benign and neoplastic prostate epithelial cells.

Drosophila Proteins↗

PubMed2000

Increased expression of fibroblast growth factor 6 in human prostatic intraepithelial neoplasia and prostate cancer.

Fibroblast growth factors (FGFs) are known to play an important role in the growth of normal prostatic epithelial cells. In addition to their effects on proliferation, FGFs can promote cell motility, increase tumor angiogenesis, and inhibit apoptosis, all of which play an important role in tumor progression. To determine whether FGFs are overexpressed in human prostate cancers, we analyzed 26 prostate cancer RNAs by reverse transcription-PCR for expression of FGF3, FGF4, and FGF6, which cannot be detected in normal prostate tissue by this technique. Fourteen of 26 prostate cancers expressed FGF6 mRNA. No expression of FGF3 or FGF4 was detected. An ELISA of tissue extracts of normal prostate, high-grade prostatic intraepithelial neoplasia (PIN), and prostate cancer for FGF6 showed that this growth factor was undetectable in normal prostate but was present at elevated levels in 4 of 9 PIN lesions and in 15 of 24 prostate cancers. Immunohistochemical analysis with anti-FGF6 antibody revealed weak staining of prostatic basal cells in normal prostate that was markedly elevated in PIN. In the prostate cancers, the majority of cases revealed expression of FGF6 by the prostate cancer cells themselves. In two cases, expression was present in prostatic stromal cells. Exogenous FGF6 was able to stimulate proliferation of primary prostatic epithelial and stromal cells, immortalized prostatic epithelial cells, and prostate cancer cell lines in tissue culture. FGF receptor 4, which is the most potent FGF receptor for FGF6, is expressed in the human prostate in vivo and in all of the cultured cell lines. Thus, FGF6 is increased in PIN and prostate cancer and can promote the proliferation of the transformed prostatic epithelial cells via paracrine and autocrine mechanisms.

Cell Division↗

PubMed2005

Increased expression of prostate-specific G-protein-coupled receptor in human prostate intraepithelial neoplasia and prostate cancers.

The G-protein-coupled receptors and signal transduction pathways represent important specific targets for a variety of human diseases, ranging from the control of blood pressure, allergic response, hormonal disorders and neurologic diseases to tumorigenesis. Most recently, we and others have identified a novel human prostate-specific G-protein coupled receptor (PSGR). To investigate the potential roles of PSGR in human normal prostate and prostate cancers, we examined the expression level of PSGR in 146 human prostate samples with real-time quantitative reverse transcription-PCR and in situ hybridization method. We significantly extended previous studies and demonstrated that PSGR is specifically expressed in human prostate tissues, not in any other normal and tumor samples tested. Compared to normal and benign prostatic hyperplasia tissues, the expression of PSGR increased significantly in human prostate intraepithelial neoplasia (PIN) and prostate tumors (approximately 10-fold), especially in early prostate tumors, suggesting PSGR may play an important role in early prostate cancer development and progression. The sensitivity and specificity estimates for PSGR expression were calculated as the area under the receiver-operating characteristics curve (0.902), indicating high-level sensitivity and specificity for discriminating benign prostate tissues from malignant prostate tissues. The association of PSGR expression with clinical parameters (clinical stages, Gleason scores, recurrent status and metastasis) was also investigated in this study. Our data suggest that overexpression of PSGR in human PIN and prostate cancers have the potential for early prostate cancer detection and diagnosis.

Aged↗

PubMed2004

PC cell-derived growth factor expression in prostatic intraepithelial neoplasia and prostatic adenocarcinoma.

PURPOSE: PCDGF (PC cell-derived growth factor), also called progranulin, is a M(r) 88000 glycoprotein precursor of granulin. It is a novel growth factor that stimulates cell proliferation, confers epithelial tumorigenesis, and promotes tumor invasion. Here we investigate the potential of PCDGF as a therapeutic target for prostate cancer. EXPERIMENTAL DESIGN: We studied the expression of PCDGF in invasive prostate cancer, adjacent high-grade prostatic intraepithelial neoplasia (PIN), and benign prostate tissue from 99 human prostate specimens. The level of PCDGF expression was correlated with various clinicopathological characteristics. RESULTS: Normal prostate tissue did not express (53/99), or expressed low levels (46/99) of PCDGF. In the 46 normal prostate specimens that expressed PCDGF, most of them had less than 10% of cells expressing PCDGF. PCDGF expression could be detected in more than 50% of cells in all specimens of PIN and invasive prostate cancer. The expression of PCDGF in normal prostate tissue was much less intense and in a smaller fraction of cells than in PIN and invasive adenocarcinoma (P < 0.0001). There was no correlation of PCDGF expression with age, Gleason score, pathological stage, status of lymph node metastasis, extraprostatic extension, perineural invasion, surgical margins, and vascular invasion. CONCLUSIONS: Our data suggest that the induction of PCDGF expression occurs during the development of PIN. PCDGF may be a new molecular target for the treatment and prevention of prostate cancer.

Adenocarcinoma↗

PubMed2003

High prevalence of human cytomegalovirus in prostatic intraepithelial neoplasia and prostatic carcinoma.

PURPOSE: Recent epidemiological data indicate that a history of increased exposure to sexually transmitted diseases is associated with an increased risk of prostate cancer. Human cytomegalovirus (HCMV) is a member of the herpesvirus family, is sexually transmitted in adults and can persistently infect prostatic epithelium in non-immunocompromised hosts. Based on increased awareness of the oncogenic potential of this virus, we decided to reexplore the issue of whether HCMV might be involved in prostate cancer pathogenesis. MATERIALS AND METHODS: Paraffin embedded biopsy specimens from 22 randomly selected patients with prostatic intraepithelial neoplasia (PIN) lesions and prostatic carcinoma were analyzed by immunohistochemistry, in situ hybridization, polymerase chain reaction and DNA sequencing to detect HCMV nucleic acids and determine whether HCMV gene products were specifically associated with neoplastic cells. RESULTS: We detected HCMV proteins and/or nucleic acids in all 22 of the 22 preneoplastic and neoplastic prostate lesions evaluated. HCMV proteins were specifically and often highly expressed in basal cell hyperplasia and PIN lesions, and to a lesser degree in carcinoma cells. RESULTS: To our knowledge these data demonstrate for the first time the specific localization of HCMV nucleic acids and proteins in a high percent of PIN and prostate carcinoma lesions, and raise the possibility that HCMV might contribute to the natural history of prostatic cancer.

Antibodies, Monoclonal↗

PubMed1993

Concordance of DNA content between prostatic intraepithelial neoplasia and concomitant invasive carcinoma. Evidence that prostatic intraepithelial neoplasia is a precursor of invasive prostatic carcinoma.

It has been postulated that prostatic intraepithelial neoplasia (PIN) is a precursor lesion to invasive carcinoma in the prostate, yet there has been little direct evidence for this relationship. Therefore, we studied the DNA content of the epithelial cells in PIN lesions with accompanying invasive carcinoma in seven cases. DNA content of nuclei in Feulgen-stained tissue sections was performed using the CAS200 System (Cell Analysis Systems Inc, Elmhurst, Ill), with normal and hyperplastic glands serving as controls for diploid DNA content. In four cases, the cells of both lesions (PIN and invasive carcinoma) contained only diploid DNA; in one case, an additional aneuploid tumor stem line was present only in the invasive component; and in two cases, both PIN and carcinoma cells contained aneuploid cells having similar DNA content. The concordance of DNA content between PIN and invasive carcinoma in these cases provides evidence that PIN is a precursor lesion for invasive carcinoma.

Adenocarcinoma↗

PubMed1998

Prostatic intraepithelial neoplasia and prostate cancer: analytical evaluation.

For urologists and pathologists one of the two main issues in prostate pathology is the identification of those prognostic factors that could predict the exact outcome of individual patients with prostate cancer (PC). Therefore, the goal is to tailor the therapeutic approach to the clinical, morphological and biological features of each patient. The other issue involves the early detection of PC, preferably in the preinvasive phase, in order to treat the patient efficaciously. For this reason, understanding the biology of preinvasive or precursors lesions has become increasingly important. Prostatic intraepithelial neoplasia is only one of these lesions, and the best known to date. The role of others, such as atypical adenomatous hyperplasia, is considered as worth exploring. Prostatic intraepithelial neoplasia (PIN) represents the putative precancerous end of the morphologic continuum of cellular proliferations within prostatic ducts and acini. Two grades of PIN are identified (low grade and high grade), and high grade PIN is considered the direct precursor of invasive carcinoma. The continuum which culminates in high grade PIN and early invasive cancer is characterised by basal cell layer disruption, basement membrane disruption, progressive loss of markers of secretory differentiation, increasing nuclear and nucleolar abnormalities, increasing proliferative potential, and increasing variation in DNA content (aneuploidy). Clinical studies suggest that PIN predates carcinoma by ten years or more, with low grade PIN first emerging in men in the third decade of life. The clinical importance of recognising PIN is based on its strong association with carcinoma; its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. The issue of precursors of prostate cancer has several facets which reflect the multiplicity of patterns and variants of PC. A big step forward in understanding some basic aspects has already been made, especially in relation to PIN. More will be available soon. A large contribution to the management of isolated PiN lesions found in prostate biopsies is expected from molecular pathology and quantitation analysis.

Journal Article↗