UMLS:C0282612 - FACTA Search

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Query: UMLS:C0282612 (PIN)
2,291 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human papillomavirus (HPV) infections are strongly linked to the pathogenesis of uterine cervical neoplasms, and have been implicated in other cancers of the female genital tract. In contrast, the association of HPV with the cancers of the male urogenital tract is less evident, except in anal and penile cancers. However, recent studies reporting the prevalence of HPV infections in human prostate cancers (60-100% HPV 16 positive vs. no infection of HPV) have raised controversies regarding the prevalence of HPV in benign and neoplastic human prostate. We investigated the prevalence of HPV infections in prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinomas in 23 surgically resected prostates. Polymerase chain reaction (PCR) was used to amplify HPV 6b/11, 16, and 18 specific DNA sequences, using type specific HPV primers selected from the transforming gene E6-E7. The areas of PIN and cancer in 6 microns H&E stained tissue sections were identified, and respective areas of PIN and cancer were isolated from the adjacent serial sections and used for DNA amplification and HPV detection (Fig. 1). Our results demonstrated the presence of HPV 16 in three carcinomas (13%), using type specific primers in PCR amplified samples. We were not able to demonstrate the presence of other HPV types (HPV 6b/11 or HPV 18) in any of the samples using specific primers. Two of these prostates showed relatively strong positive signals by dot blot analysis, when hybridized with a 32P-labeled HPV 16 type specific oligonucleotide probe. One more sample showed weak positivity, when hybridized with a 32P-labeled HPV 16 type specific oligonucleotide probe. Subsequently, we have confirmed these results by Southern hybridization of the samples transferred to nylon membrane after agarose gel electrophoresis and detected by HPV 16 type specific oligonucleotide probe, using chemiluminescent assay. We, therefore, conclude that HPV infections of the prostate in general are not as common as has been previously claimed by other investigators.
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PMID:Detection of human papillomavirus (HPV) DNA in human prostatic tissues by polymerase chain reaction (PCR). 838 63

High-grade prostatic intraepithelial neoplasia (PIN) is characterized by cellular proliferations within pre-existing ducts and glands with cytologic changes mimicking adenocarcinoma, including prominent nucleoli, but lacking stromal invasion. To determine the architectural spectrum of high-grade PIN, 60 serially sectioned radical prostatectomy specimens with PIN and cancer were reviewed. Four common patterns of high-grade PIN were identified, usually with multiple patterns in each case: tufting (in 87% of cases), micropapillary (in 85% of cases), cribriform (in 32% of cases), and flat (in 28% of cases). Tumor grade was not significantly associated with any pattern of PIN. Luminal cytoplasmic apical blebs were found in all cases regardless of the pattern of PIN. A variety of associated architectural and cytologic features were observed with high-grade PIN: epithelial arches (in 60% of cases), cellular trabecular epithelial bars (in 22% of cases), "Roman" bridges (in 30% of cases), partial gland involvement (in 82% of cases), basal cell layer disruption with glandular budding (in 23% of cases), large cystic gland involvement (in 10% of cases), involvement by nodular hyperplasia (in 5% of cases), microcalcifications (in 8% of cases), proteinaceous luminal secretions (in 62% of cases), corpora amylacea (in 55% of cases), exfoliated cells of PIN (in 42% of cases), luminal crystalloids (in 3% of cases), and mucinous metaplasia (in 2% of cases). High-grade PIN exhibits a variety of architectural patterns while retaining the distinctive cytoplasmic apical blebs and diagnostic nuclear and nucleolar features. Identification of high-grade PIN warrants a further search for invasive carcinoma, but should not influence or dictate decisions regarding definitive therapy.
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PMID:Architectural patterns of high-grade prostatic intraepithelial neoplasia. 845 75

The morphologic changes induced by neoadjuvant combination endocrine therapy were evaluated in prostatectomy specimens from patients diagnosed with localized prostate cancer. These patients participated in a prospective, randomized clinical trial investigating the effect of 3 months of combination therapy with flutamide and an LHRH agonist prior to radical prostatectomy versus radical prostatectomy alone. Ninety-six radical prostatectomy specimens processed according to the same protocol were evaluated without knowledge of prior treatment. Forty-seven patients were randomly assigned to the neoadjuvant combination therapy group and 49 to the control arm. Compared with the control group, several changes were strongly and significantly associated with exposure to neoadjuvant combination therapy. The nonmalignant prostatic tissue showed strong prominence and hyperplasia of the basal cell layer, accompanied by epithelial cell vacuolization and markedly reduced occurrence of prostatic intraepithelial neoplasia (p < 0.001) after combination therapy. Prostate cancer tissue, on the other hand, showed smaller nucleoli (p < 0.001), cell vacuolization (p < 0.001), rare intraluminal crystalloids (p < 0.001), higher Gleason grade (p < 0.001), lower prevalence of capsular penetration (p < 0.001), and less frequent invasion of the perineural spaces (p < 0.001) and surgical margins (p = 0.002). Tumor volume, was also reduced by more than 40% in the treated group (p = 0.007). The present findings show that preoperative endocrine combination therapy induces highly characteristic changes in both nonmalignant and cancerous prostatic tissue. Furthermore, following endocrine treatment, the surgical margins are less likely to be involved by cancer and capsular penetration is reduced.
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PMID:Effect of neoadjuvant endocrine therapy (combined androgen blockade) on normal prostate and prostatic carcinoma. A randomized study. 854 Jun 13

Prostatic secretions are formed by glands composed of basal and luminal cells and surrounded by a basal lamina. The normal basal cells express several integrins (extracellular matrix receptors) including alpha 2, 3, 4, 5, 6, v, beta 1 and beta 4. These integrin units are polarized at the base of the cells adjacent to the basal lamina. The integrin alpha 6 beta 4 is associated with hemidesmosomal-like structures. The natural history of prostate cancer involves the presence of prostatic intraepithelial neoplasia (PIN) lesions (considered precursor lesions), carcinoma in situ and invasive carcinoma. Hemidesmosomal proteins and the alpha 3 beta 1 and alpha 6 beta 1 integrins (laminin receptors) are retained in the early PIN lesions. Expression of the integrins alpha 2, alpha 4, alpha 5, alpha v and beta 4 is lost in carcinoma. The alpha 3 beta 1 and alpha 6 beta 1 integrins remain associated with invasive carcinoma, the latter being predominant. Integrin expression in carcinoma is diffuse in the plasma membrane and not restricted to the basal aspects of the cell. The alpha 6 beta 1 integrin is fully functional as judged by an ability to adhere to laminin and contains the wild type alpha 6A cytoplasmic signaling domain. The alpha 6 beta 1 integrin is a leading candidate for conferring the invasive phenotype in prostatic carcinoma. Tumor cells with high expression of alpha 6 integrin are more invasive when tested in a SCID mouse model system. Following intraperitoneal injection, the human tumor cells invade the mouse diaphragm and move through the muscle on the surface of the laminin coated muscle cells. Our current working hypothesis is that the production of alpha 6 beta 1 and laminin in human tumor cells contributes to the invasive phenotype. Invasion could occur on the surfaces of laminin coated structures such as the nerves, blood vessels or muscle and account for the known patterns of human prostate tumor progression. Blockage of the expression or function of alpha 6 beta 1 or laminin or preventing the loss of beta 4 would be essential steps in confining the carcinoma to the prostate gland where conventional treatment has already proven effective.
Cancer Metastasis Rev 1995 Sep
PMID:The alpha 6 beta 1 and alpha 6 beta 4 integrins in human prostate cancer progression. 854 70

Preneoplastic lesions, early neoplastic lesions and carcinomas in situ have been demonstrated to be of great value for many purposes in many organ systems. Their recognition can be useful in epidemiological studies and can facilitate the selection of patients for therapeutic interventions. They can be used as "surrogate endpoint biomarkers" in studies aimed at the chemoprevention of cancers. In the lung, colon and various other organs, such markers are well recognized to be associated with the development of cancer in man. In the livers and colons of experimental animals, there has been detailed characterization of "enzyme-altered foci" (EAF) as "putative preneoplastic markers." The words "surrogate" and "putative" are important; the biological potential of these lesions needs to be elucidated in much greater detail. The quantification of early lesions that are associated with and sometimes precursors of neoplasia is of particular value because they are much more numerous, in most organ systems, than the carcinomas that develop in the same organs. The most abundant of these lesions show minimal or no morphological alterations. For example, EAF and aberrant crypts are more numerous than polyps in the colons of patients and experimental animals with cancer or precancerous conditions that affect the colon. Currently, there are few well documented putative or surrogate markers that are highly associated with the development of prostatic carcinoma in man. The best documented among these is prostatic intraepithelial neoplasia. We have recently reported the identification of EAF in the human prostate. While they share many phenotypic alterations with prostatic intraepithelial neoplasia, much remains to be accomplished if their biological fate is to be understood.
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PMID:Prostatic intraepithelial neoplasia and other changes during promotion and progression. 860 63

The status of the basement membrane in prostatic intraepithelial neoplasia (PIN) and adenocarcinoma is unsettled. Previous studies using antibodies directed against Type IV collagen have been hindered by intense staining around the stromal smooth muscle fibers, making interpretation of acinar staining difficult. We employed a monoclonal antibody to heparan sulfate proteoglycan (HSPG) to overcome this problem, recognizing that HSPG is present in the basement membrane of epithelial and endothelial cells, but not stromal smooth muscle cells. In 22 totally-embedded whole mount radical prostatectomies for adenocarcinoma which contained PIN, intense HSPG immunoreactivity was observed in the basement membrane of all normal and hyperplastic acini, 98% of acini with high grade PIN, and 100% of acini of well differentiated (Gleason score 5) adenocarcinoma; vessels served as the internal positive control, with consistent staining throughout each specimen. The extent of HSPG immunoreactivity in cancer decreased with increasing Gleason grade (measured as percent of acini staining, in 10% increments; p = 0.002). These findings indicate that HSPG is a consistent component of the basement membrane of benign, hyperplastic, and early neoplastic prostatic acini, and, unlike other extracellular matrix proteins such as type IV collagen, is not hindered by background staining around stromal smooth muscle cells. High grade PIN and well differentiated adenocarcinoma usually maintain an intact basement membrane, and loss of the basement membrane occurs with histologic dedifferentiation.
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PMID:Prostatic intraepithelial neoplasia and well differentiated adenocarcinoma maintain an intact basement membrane. 860 64

High grade prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia (AAH) are considered putative precursors of prostatic adenocarcinoma. We determined the extent and zonal distribution of PIN and AAH in totally-embedded radical prostatectomies with prostate cancer, including 195 cases with PIN and 217 with AAH. PIN was identified in 86% of the cases. The mean volume of PIN was 1.32 cc (range, 0-8.12 cc), and was greater for PIN within 2 mm of cancer (mean, 1.0 cc) than for PIN more than 2 mm from cancer (mean, 0.3 cc). PIN was usually multicentric (64.5% of cases) and located in the non-transition zone (63%) or all zones (36%). The volume of PIN was positively correlated with the volume of cancer, patient age, pathologic stage and Gleason score. AAH was identified in 23.0% of the cases, and was more frequent in the transition zone (19.8% of cases) than in the non-transition (peripheral and central) zone (6.0%). The number of foci of AAH in the transition zone was always greater than that in the non-transition zone. AAH was frequently multicentric (46% of cases), especially in the transition zone (47% of transition zone cases) compared with the non-transition zone (23% of non-transition zone cases). The mean volume of AAH was 0.029 cc (range, 0-1.29 cc), and was much higher in the transition zone than in the non-transition zone. AAH was more common in older patients and those with greater prostatic weight, higher prostatic volume, greater percent of nodular hyperplasia, greater volume of cancer, greater percent of Gleason patterns 4 and 5 cancer, higher volume of prostatic intraepithelial neoplasia and higher serum prostate specific antigen concentration. Our results indicate that the extent and zonal distribution of high grade PIN and carcinoma are strongly associated, and that PIN is frequently multicentric; this supports the hypothesis that PIN is a premalignant lesion. AAH and carcinoma show a weak but significant association; if AAH is a premalignant lesion, it probably is associated with a subset of cancers arising in the transition zone.
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PMID:The extent and zonal location of prostatic intraepithelial neoplasia and atypical adenomatous hyperplasia: relationship with carcinoma in radical prostatectomy specimens. 860 66

The frequency and location of apoptotic bodies (AB) were evaluated in hematoxylin- and eosin-stained sections of 12 radical prostatectomies from patients with prostatic adenocarcinoma pre-treated for 3 months with total androgen ablation. Results were compared with an untreated age-, morphology- and stage-matched control group. Treated prostates showed involutional changes, with cytoplasmic vacuolization and chromatin changes ranging from mild to severe condensation, similar to that observed in apoptosis. In treated benign prostatic epithelium, the mean number of AB was 1.64% (standard error (SE), 0.19%), 6.3 times greater than in the untreated group (mean, 0.26%; SE, 0.03%). AB were more frequent in the basal cell layer than in the lumenal cell layer, whereas in the untreated group, AB were almost exclusively found in the basal cell layer. In treated prostatic intraepithelial neoplasia (PIN present in 10 cases), the mean number of AB was 1.74% (SE, 0.04%), which was 2.56 and 2.32 times greater than in untreated low grade PIN (mean, 0.68%; SE, 0.15%) and high grade PIN (mean, 0.75%; SE, 0.11%), respectively. In treated and untreated PIN, the number of AB was greatest in the basal cell layer, less in the intermediate cell layer and lowest in the cell layer bordering the lumen. The mean number of AB in the 12 treated cancers was 1.35 times greater than in untreated cancers (1.80% [SE, 0.12%] versus 1.33% [SE, 0.32%], respectively). The number of AB in treated cases of the acinar pattern of cancer (present in 7 cancer cases) was 1.78 times greater than in untreated cases, and in treated cases of the cribriform pattern of cancer (present in four cases), the mean number of AB was 1.39 times greater than in untreated cases. The number of AB was greatest in the outermost cell layer, with progressive decrease in layers closer to the lumen. In the one treated case with solid/trabecular pattern of cancer, the number of AB was 1.08 times greater than in untreated cases. The gland lumina was rich in macrophages, sloughed secretory cells with degenerative features and AB. The number of AB in the lumina increased from normal epithelium through PIN to cancer, and was greater in treated cases than in untreated cases.
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PMID:Apoptotic bodies in prostatic intraepithelial neoplasia and prostatic adenocarcinoma following total androgen ablation. 860 68

To investigate possible cell kinetic relations between benign prostatic hyperplasia (BPH), atypical adenomatous hyperplasia (AAH), prostatic intraepithelial neoplasia (PIN) and carcinoma, cell kinetic analyses were performed using radiolabelled DNA-precursors (3H-thymidine autoradiography), immunohistochemistry (proliferation marker Ki67/MIB1 and/or PCNA) and silver staining of nucleolar organizer regions (AgNOR). All methods yielded the lowest values for BPH and AAH, while maximal values were found in carcinoma of high malignancy. PIN was equal to GII-carcinomas, while AAH was between BPH and carcinoma of low malignancy. This investigation ranks BPH, AAH, low grade carcinoma, PIN and high grade carcinoma in order using different methods of cell kinetic analysis. The preneoplastic character of PIN is apparent whereas the character of AAH remains uncertain.
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PMID:Cell kinetic studies on prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia (AAH) of the prostate. 860 72

Early detection and management of prostatic cancer (PC) is an important public health problem in all industrialized countries, where the relative rate of the elderly population is rapidly increasing. We examined the epidemiology of PC in the province of Trieste, Italy and studied the relationship between prostatic intraepithelial neoplasia (PIN) and PC. The average annual incidence of PC was 99.3 per 100,000 (1,739 new prostatic cancer cases were histologically diagnosed at autopsy or in surgical specimens between 1980 and 1993). In patients over 85 years of age, the incidence rate was 1,209 per 100,000 compared with 64 per 100,000 in the 55-64 age group. Trends in PC incidence rates showed a significant increase among men under 64 years of age and those between 65-74 years. Survival analysis showed that 94% of the patients with well differentiated PC were alive at 5 years, compared with 80% and 40% of those with moderately differentiated and poorly differentiated cancer, respectively. We studied 130 whole autopsy prostates, 70 radical prostatectomies with carcinoma, 63 transurethral resections or adenomectomies without cancer from patients who later developed PC and 94 transurethral resections or adenomectomies from patients who did not develop PC. The 102 prostatic cases with cancer had a high rate of PIN, and the relative frequency of PIN 3 was high (almost 70%, versus almost 0% in benign prostates). In addition, the frequency of PIN was higher in benign prostates of patients who later developed PC (almost 50% of the cases) than in benign autopsy and surgical prostates. PIN was spatially associated with cancer in 75% of the cases. This study confirms the strong relationship between PIN and PC.
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PMID:Neoplastic and borderline lesions of the prostate: autopsy study and epidemiological data. 860 73

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