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)

Proteins encoded by bcl-2 family genes are important regulators of programmed cell death and apoptosis. Alterations in the expression of these apoptosis-regulating genes can contribute to the origins of cancer, as well as adversely influence tumor responses to chemo- and radiotherapy. Using antibodies specific for the Bcl-2, Bax, Bcl-X, and Mcl-1 proteins in combination with immunohistochemical methods, we examined for the first time the expression of these bcl-2 family genes in 64 cases of adenocarcinoma of the prostate, including 10 Gleason grade 2 to 4 tumors, 21 grade 5 to 7 tumors, 17 grade 8 to 10 tumors, 8 lymph node metastases, and 8 bone metastases. In addition, 24 cases of prostatic intraepithelial neoplasia (PIN) or PIN coexisting with carcinoma were also evaluated. All immunostaining results were scored with regard to approximate percentage of positive tumor cells and relative immunostaining intensity. Expression of the anti-apoptotic protein Bcl-2 was present in 16 of 64 (25%) adenocarcinomas and tended to be more frequent in high grade tumors (Gleason grade 8 to 10; 41%) and nodal metastases (38%) than in lower grade (Gleason 2 to 7) primary tumors (16%; P < 0.05). Bcl-X was expressed in all 64 (100%) tumors evaluated. Bcl-X immunointensity was generally stronger in high grade primary tumors (grade 8 to 10) and metastases compared with PIN and low grade neoplasms (P < 0.0001). In addition, the proportion of specimens with > 50% Bcl-X-immunopositive tumor cells also was higher in advanced grade primary tumors (Gleason 8 to 10) and metastases than in PIN and low grade tumors (Gleason 2 to 7; P < 0.005). The anti-apoptotic protein Mcl-1 was expressed in 52 of 64 (81%) tumors, compared with only 9 of 24 (38%) cases of PIN (P < 0.001). In addition, the percentage of Mcl-1-positive cells was typically higher in Gleason grade 8 to 10 tumors and metastases than in PIN or lower grade tumors (P = 0.025). In contrast, the pro-apoptotic protein Bax was expressed in all prostate cancers evaluated, with high percentages of immunopositive cells and strong immunointensity typically occurring regardless of tumor grade. The findings suggest that expression of several anti-apoptotic members of the bcl-2 gene family, including bcl-2, bcl-X, and mcl-1 increases during progression of prostate cancers, a finding that may be relevant to the hormone-insensitive, metastatic phenotype of most advanced adenocarcinomas of the prostate.
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PMID:Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers. 862 25

Prostatic intraepithelial neoplasia (PIN) fulfils the majority of requirements for a premalignant change in the human prostate. Forty-eight patients were diagnosed to have high grade PIN on prostatic needle biopsy. During a follow-up period, 23 (47.9%) were found to have adenocarcinoma on subsequent biopsies. We compared the patients age, the digital examination, the transrectal ultrasound appearance (TRUS) and the serum PSA level between those in whom cancer was detected subsequently and those with PIN alone. There was a statistically significant difference in the transrectal ultrasound appearance (TRUS) and the serum PSA level between the two groups (p < 0.001, p < 0.016 respectively). In conclusion, patients with high grade PIN, elevated serum PSA with hypoechoic zone on TRUS should be rebiopsied 3 months after the initial diagnosis. If the results are negative, close follow-up is mandatory.
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PMID:[High-grade intraepithelial prostatic neoplasms: diagnosis and association with prostate cancer]. 865 30

A-80 is a mucin-like glycoprotein associated with exocrine differentiation that shows little or no expression in normal exocrine cells and typical adenomas, but is upregulated in dysplasia and adenocarcinoma of certain organs. Its expression has not been systematically examined in prostatic adenocarcinoma and its putative precursor, prostatic intraepithelial neoplasia (PIN). The authors applied a mouse monoclonal antibody against A-80 in paraffin-embedded sections from 103 cases of prostatic carcinoma, 26 cases of nodular hyperplasia, 7 autopsy samples from normal young adult prostates, and 12 fetal prostates. All but one cancer reacted, although expression was heterogeneous; 75 of 103 stained extensively (> 3+ on a 0 to 5+ scale) and strongly. Staining extent and intensity were independent of tumor grade, and tended to be strong even when focal. Seventy-seven of 84 foci (92%) of high-grade PIN and 38 of 52 foci (73%) of low-grade PIN stained for A-80; reactions were most extensive and intense in high grade PIN. Only 5 of 26 cases (19%) of hyperplasia reacted, and this consisted of weak to moderate staining in sporadic cells; the remainder were negative. Normal adult prostatic epithelium did not express A-80 except for weak and inconsistent staining in foci of inflammation and infarction; atrophic glands were negative. Fetal prostate showed focally strong reactivity. These results indicate that A-80 is selectively expressed in most cases of intraepithelial neoplasia and prostate cancer, but is usually absent in benign and hyperplastic epithelium. The upregulation of glycoprotein A-80 in PIN and adenocarcinoma parallels observations in other organs, such as the breast and colon, suggesting that this is a significant oncodevelopmental molecule with potential clinical applications.
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PMID:Immunolocalization of glycoprotein A-80 in prostatic carcinoma and prostatic intraepithelial neoplasia. 866 63

Malignant epithelial masses within prostatic duct lumens have been equated with several conflicting entities, including Gleason cribriform grade 3 carcinoma and cribriforming dysplasia. We identified 51 radical prostatectomy cancers containing intraductal lesions among 130 cases, with total cancer volumes between 4 and 10 cc. Such lesions with duct lumen-spanning septa or masses were rare in areas away from invasive cancer (22 foci), while dysplasia (prostatic intraepithelial neoplasia) was common (1,490 foci). Consequently, these lesions were interpreted as being part of the evolution of invasive carcinoma rather than precursors; they were designated "intraductal carcinoma" as distinct from dysplasia. Intraductal cancer areas within invasive carcinoma usually represented cancer extension within the branches of a single segment of the duct-acinar system from near the urethra to the gland capsule. In 51% of cases with intraductal spread, the invasive component produced large ( > 0.5 mm) tumor masses in perineural spaces, which in turn correlated strongly with extensive capsule penetration and frequent positive surgical margins selectively at the superior nerve pedicle. The amount of grade 4/5 cancer, the amount of intraductal carcinoma, and the large perineural tumor mass appeared to be related to postprostatectomy progression of cancer, as measured by elevation of ultrasensitive serum prostate-specific antigen. It was concluded that intraductal prostatic adenocarcinoma is a common morphologic entity with precisely defined histologic criteria and a unique biologic significance, as reflected by an enhanced capacity for extensive spread within ducts and perineural spaces. It was proposed that the diversity of diagnoses attached to most cribriform malignant lesions can be unified by the concept of this single entity.
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PMID:Spread of adenocarcinoma within prostatic ducts and acini. Morphologic and clinical correlations. 866 28

Dysplasia of prostate or prostatic intraepithelial neoplasia (PIN) is associated with prostatic adenocarcinoma, which is quite common in elderly males. The presence of high grade PIN in biopsy of patients with clinically suspicious tumors is an indication of further search for malignancy. Whole mount sections of 48 prostates were studied. PIN was sought and graded. The morphology of other lesions including atrophy, adenosis and basal cell hyperplasia, and also seminal vesicle epithelium was studied. All 36 prostates resected for treatment of prostatic adenocarcinoma contained foci of PIN. The differential diagnosis of PIN, atrophy, adenosis, basal cell hyperplasia and seminal vesicle epithelium is quite easy when whole mount sections are studied. Whole mount sections of prostates are valuable teaching material for pathologists.
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PMID:Diagnosis of prostatic intraepithelial neoplasia in whole mount sections of prostates. 867 35

High-grade PIN is the most likely precursor of prostatic adenocarcinoma, according to virtually all available evidence to date. The clinical importance of recognizing PIN is based on its strong association with prostatic carcinoma. PIN has a high predictive value as a marker for adenocarcinoma. Its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma. PIN is associated with progressive abnormalities of phenotype and genotype intermediate between normal prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. There is progressive gain or loss of a wide variety of biomarkers, including morphometric markers, differentiation markers, stromal markers, growth factors and associated receptors, oncogenes, tumor suppressor genes, and chromosomes. Abnormalities in expression of most biomarkers are amplified in the progression from high-grade PIN to localized cancer, metastatic cancer, and hormone-refractory cancer. Oncogenesis of prostatic carcinoma probably occurs through the selection of several genetic changes, each modifying the expression or function of genes controlling cell growth and differentiation. Further studies are needed to evaluate the function and prognostic value of oncogene expression in the normal, preneoplastic, and neoplastic prostate.
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PMID:Molecular biology of prostatic intraepithelial neoplasia. 870 Aug 1

Overexpression of the nm23H1 gene has been associated with the suppression of metastasis in several solid tumors. However, in colorectal carcinoma and neuroblastoma, increased levels of nm23 H1 nucleoside diphosphate kinase A (NDPKA) mRNA are associated with tumorigenesis. To determine the role of nm23 H1/NDPKA in the prostate, normal and/or malignant tissue samples from 29 consecutive patients were studied. Levels of nm23 H1/NDPKA mRNA and nm23 H1/NDPKA mRNA protein were determined in tissue from 18 and 27 patients, respectively. In all, 16 of the 18 tumor samples expressed increased levels of nm23 H1/NDPKA mRNA as compared with those measured in normal tissue. The level of nm23 H1/NDPKA mRNA was > 10-fold higher in a metastatic lymph node than in normal prostate tissue. All cancer specimens and areas of prostatic intraepithelial neoplasia showed immunoreactivity with the nm23 H1/NDPKA antibody; however, normal prostatic tissue was unreactive. These findings suggest that overexpression of the nm23 H1/NDPKA gene occurs frequently in adeno-carcinomas of the prostate and may be an early event in prostate cancer tumorigenesis.
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PMID:Increased levels of nm23 H1/nucleoside diphosphate kinase A mRNA associated with adenocarcinoma of the prostate. 873 6

Controversies abound in relation to the treatment of every stage of prostate cancer and its natural history. We critically evaluate the controversies and information that exist. An ongoing autopsy project at Wayne State University aims to: define the prevalence of incidental cancer in subjects between 20 and 70 years of age; study the potential difference between Caucasians and Blacks; and to analyze other associated histological lesions such as prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia. Initial results note that there was only a weak correlation between high-grade PIN and incidental carcinoma, both lesions started to present at an early age with a progressive increase after the seventh decade, and there was no racial difference observed among Caucasians and African-American males. These results pose several questions which need further explanation. Most studies use digitorectal examination, transrectal 7-MHz ultrasonography and prostate-specific antigen for the early diagnosis of prostate cancer, we attempt to determine the best and most economical combination presently available. In discussing the therapeutic options for patients with localized prostate cancer, we review our personal experience with surgery and radiotherapy.
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PMID:Issues on early diagnosis and treatment of localized prostate cancer. 877 10

Prostatic intraepithelial neoplasia (PIN) is regarded as a precursor lesion of at least some prostatic cancers. Using interphase cytogenetics, an in situ hybridization technique with chromosome specific probes, we investigated 15 prostatectomy specimens containing both invasive carcinoma and PIN for the presence of numerical changes of chromosomes 7, 8, 10, 17 and X. The results were correlated with tumor stage and Gleason grade as well as with morphological features of PIN. Of the 15 carcinomas, four were disomic, five displayed at least focal chromosomal gains and six were found to be aneusomic. A non-disomic chromosomal status correlated well with a higher tumor stage and grade. Although the majority of PIN glands showed an eusomy, focal chromosomal gains within single glands or parts of a gland could be observed in 12 of the 15 cases. All but one specimen with non-disomic carcinomas also harboured areas of PIN with numerical chromosomal aberrations, often laying directly adjacent to tumorous glands. Additionally, focal non-disomies of PIN could also be detected in two cases with eusomic cancer. With regard to numerical changes in PIN and cancer, no significant preponderance could be observed for the five chromosomes tested. We conclude that numerical chromosomal aberrations are a frequent, but mostly focal event in PIN. This karyotypic instability is further evidence for the premalignant nature of this lesion.
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PMID:Numerical chromosomal changes in high-grade prostatic intraepithelial neoplasia (PIN) and concomitant invasive carcinoma. 883 46

Acinar carcinoma of the prostate is the third most frequently registered cancer and its incidence is expected to increase as life expectancy increases. Consequently, there have been attempts to introduce possible screening programmes for early detection of prostatic carcinoma. In this context the histopathologist has a role in that potential pre-neoplastic lesions have to be recognized. Two such pre-neoplastic lesions in the prostate are adenomatous hyperplasia and prostatic intraepithelial neoplasia. In this article the histological features of these lesions, their differential diagnosis and their pre-malignant potential are reviewed.
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PMID:Pre-neoplastic lesions of the prostate. 884 60


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