Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0282612 (PIN)
 2,291 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Significance of high-grade prostatic intraepithelial neoplasia on prostate biopsy. 1285 44

NSAID-activated gene (NAG-1) protein was previously identified by microarray analysis as overexpressed in prostate cancer. We performed immunohistochemistry and Western blotting with rabbit polyclonal antibody to NAG-1. Fifty malignant tissues obtained by prostatectomy and 17 from benign cases were compiled. Cancer tissues included Gleason scores 3-6, 3+4=7, 4+3=7, and 8-10. Cancer and high-grade prostatic intraepithelial neoplasia (PIN) consistently showed moderate to intense cytoplasmic reactivity in 95-100% of epithelium. Staining intensity inversely correlated with preoperative serum prostate-specific antigen (PSA) (p=0.005) and with grade, averaging (on a 0 to 3+ scale) 2.3 +/- 0.6 in the lowest grade group, and 2.0 +/- 0.7, 1.8 +/- 0.5, and 1.5 +/- 0.6 as grade increased (p<0.008). Benign epithelium was nonreactive in 17/17 specimens without concurrent cancer (11 transurethral resection, 2 enucleation, 4 biopsy, p=0.002). Decreased NAG-1 expression in higher grade cancer is consistent with its known antitumorigenic, proapoptotic activities.
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PMID:Overexpression of NSAID-activated gene product in prostate cancer. 1289 47

The purpose of this article is to evaluate color Doppler imaging (CDI) as an adjunctive tool to gray-scale ultrasound (US) in the diagnosis of prostate cancer and to correlate CDI-positive lesions to cancer grade. We retrospectively analyzed 619 consecutive patients who underwent prostate US, CDI, and biopsy because of abnormal digital rectal examination results or prostate-specific antigen levels. All had directed (into a specific lesion) biopsies or directed biopsies along with systematic four-quadrant or sextant biopsies, or systematic biopsy alone. Color Doppler imaging was compared with gray-scale findings and histologic results. There were 222 (35.9%) biopsy-proven cancers (n = 197) or prostatic intraepithelial neoplasia (n = 25). Of these, 106 (47.7%) had color-flow abnormalities. Of these 106 patients, 26 (24.5%), or 11.7% of all cancer patients, had relatively normal gray-scale US findings but had focal CDI abnormalities as the method of identification. Overall, 76.9% of these were moderate to high Gleason grades and were considered clinically significant lesions. Color Doppler imaging can identify a large number (11.7%) of clinically significant prostate cancers that are poorly seen by gray-scale US. Positive lesions on CDI are of clinical importance because 76.9% are histologically, moderately, or poorly differentiated. We recommend that CDI be used in all diagnostic and biopsy-guided US examinations of the prostate.
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PMID:Color Doppler imaging of the prostate: important adjunct to endorectal ultrasound of the prostate in the diagnosis of prostate cancer. 1297 76

High-grade prostatic intraepithelial neoplasia (PIN) is now accepted as the most likely preinvasive stage of adenocarcinoma, almost two decades after its first formal description. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent invasive carcinoma. The only method of detection is biopsy; PIN does not significantly elevate serum prostate-specific antigen (PSA) concentration or its derivatives and cannot be detected by current imaging techniques, including ultrasound. Most patients with PIN will develop carcinoma within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype, which are similar to cancer rather than normal prostatic epithelium, indicating impairment of cell differentiation with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.
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PMID:High-grade prostatic intraepithelial neoplasia. 1473 6

To date, several reports have been published about CpG island methylation of various genes in prostate cancer. However, most of these studies have focused on cancer tissue only or a single gene and data about concurrent methylation of multiple genes in prostate cancer or prostatic intraepithelial neoplasia (PIN) are limited. The aim of the present study was to determine the methylation profile of 11 tumour-related genes in prostate cancer and PIN. Seventy-one samples, including 37 prostate cancers, 14 PINs, and 20 normal prostates, were examined for the methylation status of 11 tumour-related genes using methylation-specific PCR. The mean number of genes methylated was significantly higher in prostate cancer and PIN than in non-neoplastic prostate (4.4, 3, and 0.2, respectively; p < 0.001). In prostate cancer, APC, GSTP1, MGMT, and RASSF1A were frequently methylated at a frequency of 56.8%, 86.5%, 75.7%, and 83.8%, respectively. These genes were methylated in more than 30% of PINs. Prostate cancers with high serum prostate-specific antigen (PSA) (more than 8 ng/ml) or a high Gleason score (GS) (3 + 4 or more) showed higher numbers of methylated genes than those with low serum PSA (8 or less) or low GS (3 + 3 or less) (5.4 versus 2.5 and 5.4 versus 3.1, respectively; p < 0.05). The methylation frequency of APC, RASSF1A, and RUNX3 was higher in prostate cancers with high serum PSA or with high GS than in those with low PSA or with low GS, respectively, the differences reaching statistical significance (p < 0.05). A strong association between MGMT methylation and loss of MGMT expression was demonstrated by immunohistochemistry. CpG island methylation is a frequent event, occurs early, and accumulates during multi-step prostatic carcinogenesis. High levels of CpG island hypermethylation might serve as a potential biological marker for aggressive prostate cancer.
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PMID:Aberrant CpG island hypermethylation of multiple genes in prostate cancer and prostatic intraepithelial neoplasia. 1474 6

The class A macrophage scavenger receptor (SR-A) is expressed in antigen presenting cells and is involved in host immune responses. Germ-line mutation of this gene has been associated with increased risk of human prostate cancer. However, there is little known about its expression in normal or neoplastic human prostate tissues. Double immunofluorescent labeling with monoclonal antibodies to SR-A and specific macrophage and dendritic cell markers was used to identify cells expressing SR-A in human prostate tissues. SR-A immunohistochemical staining was performed on paraffin sections of normal prostate, prostatic intraepithelial neoplasia (PIN) lesions, and prostate cancers from radical prostatectomy specimens. SR-A was expressed in a subset of macrophages and dendritic cells that infiltrated prostatic tissues. The majority of SR-A-positive cells coexpressed CD68, and a relatively low percentage expressed S100 protein. The number of SR-A-positive cells was significantly increased in PIN as compared with normal prostatic tissue (P = 0.0176). In contrast, the number of SR-A-positive cells decreased with tumor progression. A lower SR-A-positive cell density was associated with higher clinical stage (rho = -0.26; P = 0.0234). Inverse associations were also found between SR-A density and positive lymph nodes (rho = -0.23; P = 0.0437), tumor size (rho = -0.31; P = 0.0100) and preoperative PSA levels (rho = -0.32; P = 0.0057). SR-A density is a significant predictor of disease-free survival after surgery univariately (P = 0.0003), as well as multivariately, adjusted for known clinical and pathological markers including preoperative prostate-specific antigen, clinical stage, Gleason score, surgical margin, extraprostatic extension, and seminal vesicle invasion, as well as lymph node metastasis (P = 0.0021). The preferential accumulation of SR-A-positive cells in PIN suggests a role for SR-A in the APC response to early malignancy. A reduction in the number of SR-A-positive cells demarcates tumor progression as indicated by clinical and pathological correlations. Our results additionally indicate that systematic measurement of SR-A density is a strong prognostic marker for clinical outcome after surgery.
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PMID:Reduced infiltration of class A scavenger receptor positive antigen-presenting cells is associated with prostate cancer progression. 1502 46

Men with high-grade prostatic intraepithelial neoplasia (PIN) evident on prostate biopsy are at high risk for the eventual development of prostate cancer. The ability to reverse high-grade PIN may reduce the incidence or delay the development of prostate cancer. Toremifene (GTx-006, Acapodene trade mark ) is a selective estrogen receptor modulator that has been shown in the transgenic mouse model of prostate cancer to eliminate high-grade PIN and reduce the incidence of prostate cancer. This study was aimed at the evaluation of the safety and efficacy of toremifene in men diagnosed with high-grade PIN. This was an open-label, phase IIA clinical trial that enrolled 21 men (mean age, 64.7 years) with evidence of high-grade PIN on biopsy within 6 months of entry into the study. Eighteen of these men (86%) completed toremifene treatment (60 mg/day orally for 4 months) and then underwent follow-up prostate biopsy (8 cores) to determine high-grade PIN status. The effect of the drug on serum prostate-specific antigen (PSA), percentage of free PSA, testosterone, estradiol, and quality of life was also measured. After toremifene treatment, 72% of these 18 men (vs. 17.9% of historical controls) had no high-grade PIN on subsequent prostate biopsies. Mean PSA trended higher, and percentage of free PSA was increased. Quality of life was not significantly affected by treatment. There were 3 mild adverse events, and no serious adverse events. Toremifene appeared to reduce high-grade PIN in this small, exploratory trial. The drug was well tolerated. A double-blind, dose-finding, randomized, placebo-controlled phase IIB/III study is currently open to further study toremifene's activity against high-grade PIN and prostate cancer incidence.
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PMID:Phase IIA clinical trial to test the efficacy and safety of Toremifene in men with high-grade prostatic intraepithelial neoplasia. 1504 81

We studied 101 prostatic adenocarcinomas (72 acinar 29 ductal) and 16 cases with high-grade prostatic intraepithelial neoplasia (HPIN) immunohistochemically for the expression of beta-catenin and compared the staining patterns with those of nonneoplastic prostatic epithelium and 24 colorectal adenocarcinomas. While nuclear staining for beta-catenin was evident in 20 (83%) colorectal adenocarcinomas, predominantly, membranous staining was observed in 89 prostatic adenocarcinomas (88%); the remaining 12 cases showed no immunoreactivity. In prostatic tumors expressing beta-catenin, staining intensity was comparable, increased, and decreased in 81, 4, and 4 cases, respectively compared with adjacent nonneoplastic prostatic epithelium. No prostatic adenocarcinomas demonstrated nuclear staining. The beta-catenin staining characteristics in HPIN were comparable to those in nonneoplastic prostatic epithelium. Negative staining for cytokeratins (CKs) 7 and 20, high-molecular-weight (HMW) CK, and villin and positive staining for prostate-specific antigen (PSA) were seen in 22 prostatic adenocarcinomas examined, in contrast with colorectal adenocarcinomas, which stained positively for CK20 and villin and negatively for CK7, HMWCK, and PSA. These data suggest that the beta-catenin signaling pathway acts differently in prostatic than in colorectal tumorigenesis. The immunophenotypes documented herein also might aid in the distinction between prostatic and colorectal origins when metastasis is encountered.
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PMID:Expression of beta-catenin in prostatic adenocarcinomas: a comparison with colorectal adenocarcinomas. 1508 Mar 8

The aim of this study was to evaluate possible pedictors of the outcome of repeat random sextant biopsy of the prostate prompted by a rise in prostate-specific antigen (PSA). Random biopsies performed for PSA elevation (>4 ng/mL) in the course of a randomized study of screening efficacy were reviewed, and 87 consecutive biopsies (carcinoma = 13, high-grade prostatic intraepithelial neoplasia = 6, negative = 68) performed in subjects with a negative random biopsy at the previous screening round were considered. Findings at digital rectal examination or transrectal ultrasonography and total PSA value were not useful predictors of repeat biopsy outcome, whereas PSA velocity was significantly associated with biopsy outcome. The positive predictive value for a cancer biopsy was 2.7% (1/36), 28.5% (2/7), and 22.7% (10/44) for PSA velocity values of <0.1, 0.1-0.19, and >0.19 ng/mL/yr, respectively. A cutoff of 0.1 ng/mL/yr for PSA velocity would have allowed to avoid approximately half (35/74 = 47.2%) of the benign biopsies while decreasing the sensitivity by 7.6% (1/13), and is thus suggested as a possible criterion for the indication of repeat random biopsy for persistent PSA elevation.
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PMID:Predictors of random sextant biopsy outcome in screened men with PSA > 4 ng/mL and a negative sextant biopsy at previous screening. Experience in a population-based screening program in Florence. 1525 39

High-grade prostatic intraepithelial neoplasia (HGPIN) is commonly encountered on prostate needle biopsies and, based on epidemiologic, molecular, and animal models, has proven to be the most significant risk factor for prostate cancer and likely represents the premalignant phase of prostatic adenocarcinoma. This lesion is characterized by cellular proliferations within pre-existing ducts and glands, with nuclear and nucleolar enlargement similar to prostate cancer. However, unlike cancer, HGPIN retains a basal cell layer identifiable by immunohistochemistry with the basal cell-specific antibody cytokeratin 34bE12. The incidence of HGPIN identified in needle biopsies is as high as 25%, increases with age, and coexists with prostate cancer in approximately 85% of cases. There appears to be no causal relationship between HGPIN and serum prostate-specific antigen (total, percent free, or density) or radiographic characteristics on transrectal ultrasound. In a large series, the identification of HGPIN on initial needle biopsy is associated with about a 35% risk of prostate cancer on subsequent biopsies. Thus, the finding of HGPIN on prostate needle biopsy necessitates a second biopsy in a patient eligible for curative treatment. As a precursor lesion, HGPIN is currently a target for chemopreventive strategies, including antiandrogens and nutritional supplementation.
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PMID:Prostatic intraepithelial neoplasia: an update. 1527 87


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