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PubMed2004

Canine prostatic intraepithelial neoplasia: is the comparative model relevant?

BACKGROUND: Histologic sections from an archival collection of a veterinary teaching hospital were examined to determine the likelihood of detection of canine high-grade prostatic intraepithelial neoplasms (HGPIN), as a prelude to use of the canine model of prostatic carcinogenesis for chemopreventive strategies. METHODS: Tissue specimens representing clinically healthy (normal) prostate glands, benign prostatic hyperplasia, and prostatic carcinoma were examined in one tissue plane for histological evidence of HGPIN. RESULTS: No histological evidence of HGPIN was detected in 20 normal prostate glands or 95 prostate glands with benign prostatic hyperplasia. Seven of 20 prostatic carcinomas had synchronous HGPIN. CONCLUSIONS: Histological evidence of HGPIN is unlikely to be detected in the healthy or hyperplastic canine prostate gland with the clinically-procured biopsy. This might diminish the usefulness of canine HGPIN in temporal studies of chemoprevention of prostate cancer. HGPIN was found simultaneously with prostatic carcinoma in more than one-third of the carcinomas examined.

Animals↗
PubMed1999

Genetic and chromosomal alterations in prostatic intraepithelial neoplasia and carcinoma detected by fluorescence in situ hybridization.

OBJECTIVE: In this review, we discuss the utility of fluorescence in situ hybridization (FISH) in the determination of genetic and chromosomal alterations in prostate cancer specimens. We also discuss the genetic association between prostatic intraepithelial neoplasia (PIN) and adenocarcinoma as detected by FISH and other techniques. METHODS AND RESULTS: FISH is a commonly used technique for the determination of gene and chromosome dosage. In tissue sections, FISH allows precise histopathologic correlation of multiple foci of normal epithelium, premalignant lesions, and carcinoma within a single specimen, including study of intratumoral heterogeneity. PIN and prostatic carcinoma foci have a similar proportion of genetic changes, but foci of carcinoma usually have more alterations. This supports the hypothesis that PIN is the most likely precursor of prostatic carcinoma. The most common genetic alterations in PIN and carcinoma are: (1) gain of chromosome 7, particularly 7q31; (2) loss of 8p and gain of 8q, and (3) loss of 10q, 16q and 18q. Inactivation of tumor suppressor genes and/or overexpression of oncogenes in these regions may be important for the initiation and progression of prostate cancer. CONCLUSIONS: FISH is a useful technique to determine genetic relationships between cancer and its precursors. PIN and prostatic carcinoma foci have a similar proportion of genetic alterations, suggesting that PIN is often a precursor of prostatic carcinoma. Genes on chromosomes 7, 8, 10, 16 and 18 may play an important role in both initiation and progression of prostatic carcinoma.

Adenocarcinoma↗
PubMed1995

Immunohistochemical localization of parathyroid hormone-related protein in prostatic intraepithelial neoplasia.

Parathyroid hormone-related protein (PTHrP) is a regulatory protein hormone that has been associated with normal fetal growth and differentiation as well as fetal calcium regulation. Parathyroid hormone-related protein has been implicated in a variety of carcinomas as a major factor in the development of humoral hypercalcemia of malignancy and may also play a role as an autocrine growth factor. In a previous immunohistochemical study we found that all prostatic adenocarcinomas (CAP) express PTHrP. In the current study, we evaluated PTHrP in prostate intraepithelial neoplasia (PIN) in radical prostatectomy specimens. A validated mouse monoclonal antibody, 9H7, raised against fragment 109-141 of the carboxy-terminus of PTHrP was used for immunostaining. The results generally showed negative to weak staining of normal and hyperplastic tissue and strong staining in PIN. The staining intensity was further evaluated by computer based image analysis. The relative optical density in PIN (9.24 +/- 9.05) was significantly (P = .008) higher than that in normal gland (.00 +/- 3.6). These findings suggest that PTHrP may be involved in the pathogenesis of prostatic dysplasia, and its immunohistochemical evaluation may have diagnostic use in the evaluation of PIN.

Adenocarcinoma↗
PubMed1995

Working standards in prostatic intraepithelial neoplasia and atypical adenomatous hyperplasia.

All participants agreed with the use of the terms low and high grade PIN, without treatment in the case of an isolated PIN lesion. The term, definitions and biology of atypical adenomatous hyperplasia (AAH) was discussed without reaching a consent among American and European participants. As a compromise, the designation of AAH-Adenosis was accepted as a working formulation that needs further research.

Humans↗
PubMed2006

Risk of prostate cancer on first re-biopsy within 1 year following a diagnosis of high grade prostatic intraepithelial neoplasia is related to the number of cores sampled.

PURPOSE: We determined the influence of the extent of needle biopsy sampling on the detection rate of cancer on first biopsy within 1 year following a diagnosis of HGPIN. MATERIALS AND METHODS: We identified 791 patients with HGPIN on the initial biopsy who had a followup biopsy within 1 year of their diagnosis. The mean interval from diagnosis of HGPIN to re-biopsy was 4.6 months. In the initial biopsy with HGPIN, 323 men had 8 or more cores (median 10, range 8 to 26) and 332 men had 6 core biopsies. RESULTS: In the 6 core initial sampling group, the risk of cancer on re-biopsy was 20.8% compared to only 13.3% following an initial 8 core or more sampling (p = 0.011). With 6 core biopsies for both the initial and re-biopsy the risk of cancer was 14.1% (group 1). With an initial 6 core biopsy and 8 core or more biopsy on followup, the risk of cancer was 31.9% (group 2). With 8 core or more biopsy sampling for both initial and repeat biopsies, the risk for cancer was 14.6% (group 3). The differences between groups 1 and 3 as compared to group 2 were statistically significant (p = 0.001 and p <0.0001, respectively). CONCLUSIONS: With relatively poor sampling (6 cores) on the initial biopsy, associated cancers are missed resulting in only HGPIN on the initial biopsy, and with relatively poor sampling on re-biopsy there is also a relatively low risk of finding cancer on re-biopsy (group 1). With poor sampling on the initial biopsy and better sampling on re-biopsy, some of these initially missed cancers are detected on re-biopsy yielding a higher detection of cancer (group 2). Sampling more extensively on the initial biopsy detects many associated cancers, such that when only HGPIN is found they often represent isolated HGPIN. Therefore, re-biopsy even with good sampling does not detect many additional cancers (group 3). Our study demonstrates that the risk of cancer on biopsy within 1 year following a diagnosis of HGPIN (13.3%) is not that predictive of cancer on re-biopsy if good sampling (8 or more cores) is initially performed. For patients diagnosed with HGPIN on extended initial core sampling, a repeat biopsy within the first year is unnecessary in the absence of other clinical indicators of cancer.

Adult↗
PubMed1996

Differential histochemical peanut agglutinin stain in benign and malignant human prostate tumors: relationship with prostatic specific antigen immunostain and nuclear DNA content.

The histochemical binding pattern of the peanut (Arachis hypogaea) lectin (PNA) was quantitatively described by means of computer-assisted microscope analysis in 28 benign prostatic hyperplasias (BPH), 15 prostatic intraepithelial neoplasias (PIN), and 119 prostatic adenocarcinomas. PNA exhibits nonimmune but selective binding to glycoproteins with beta-D-galactosyl(1,3)-N-acetyl-D-galactosamine residues. We also investigated whether a relationship existed between the number of histochemical-related PNA acceptors and the histochemical prostate-specific antigen (PSA) stain intensity, and between the number of PNA receptors and DNA ploidy level. The results show that neoplastic prostate tissues and high-grade intraepithelial prostatic neoplasias (PIN2_3) exhibit a significantly higher number of PNA acceptors than benign prostatic hyperplasias and low (PIN1) grade prostatic intraepithelial neoplasias. A statistically significant correlation was observed between the number of histochemically related PNA acceptors and PSA immunostain intensity. Lastly, diploid prostatic tumors, whether benign or malignant, exhibited a significantly higher number of PNA acceptors than aneuploid ones. These results suggest that PNA acceptors play an important role in the biology of prostate tumors.

Adenocarcinoma↗
PubMed2000

[Indication and strategy for further biopsies following the diagnosis of prostatic intra-epithelial neoplasia].

Prostatic Intraepithelial Neoplasia (PIN) lesions are characterized by proliferation of the epithelial cells lining prostatic ducts and acini. Only high grade PIN lesions (grades 2 and 3) should be reported on biopsy histology reports. The authors present a review of the literature. The clinical importance of demonstration of isolated PIN lesions on prostatic biopsies is based on the high risk of associated invasive cancer present in the prostatic gland in 22% to 100% of cases, usually adjacent to the zone presenting PIN lesions. This risk increases as the grade of the PIN lesion increases, when there is a clinical (abnormal digital rectal examination) or laboratory suspicion (elevation PSA > 10 ng/ml), or in elderly patients. Identification of a high grade PIN does not require any immediate treatment decision. PSA assays do not need to be repeated. A new series of biopsies is recommended after three months. The optimal strategy for the choice of the new biopsy sites has not been defined. In the case of a first series of sextant biopsies, a new series of biopsies is recommended, combining biopsies directed towards the site of PIN lesions (3 biopsies in the site of PIN lesions, 2 biopsies adjacent to this site) and systematized biopsies of the same side. In the case of a first series of non-systematized biopsies, a new series of systematized biopsies is recommended.

Biopsy↗
PubMed1999

High-grade prostatic intraepithelial neoplasia in dogs.

The dog is the only nonhuman species in which high-grade intraepithelial neoplasia (HGPIN) and invasive carcinoma spontaneously occur. Our work was the first to describe HGPIN in the dog prostate. Canine HGPIN bears remarkable morphologic similarity to its human counterpart. There is also striking similarity between canine and human HGPIN with respect to basal layer disruption, proliferative index, and microvessel density. For each of these parameters, HGPIN is intermediate between benign epithelium and invasive carcinoma, strengthening the hypothesis that HGPIN is an intermediate step on the road to prostate cancer. In another study, we showed that HGPIN is present in the majority (55%) of elderly sexually intact pet dogs without clinical evidence of prostate cancer. These data suggest that the early events of prostate carcinogenesis may occur with high frequency within the prostates of pet dogs sharing the same environment as humans. We are currently conducting a large-scale autopsy-epidemiological study to further characterize the epidemiology of HGPIN and invasive carcinoma in pet dogs. We are also testing the potential utility of pet dogs for the rapid, cost-effective in vivo screening of chemopreventive agents by using the prevalence and extent of HGPIN in the dog prostate as a surrogate endpoint biomarker.

Animals↗