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)

Prostatic intra-epithelial neoplasia (PIN, or intraductal dysplasia) is considered a precursor of invasive carcinoma, characterized by proliferation and anaplasia of cells lining prostatic ducts and acini. The highest grade of PIN, Grade 3, is thought to represent carcinoma in situ. To quantitate the degree of disruption of the basal cell layer in human prostatic ducts and acini as a potential marker of early invasion in PIN, a monoclonal antibody to keratin proteins of 49, 51, 57, and 66 kd which selectively labels the prostatic basal cell layer was used. A total of 1093 acini with PIN were identified in 14 cases with invasive carcinoma. Tumor cells consistently failed to be decorated with this antibody. The frequency of disruption of the basal cell layer increased with increasing grades of PIN, with disruption present in 0.7% of cases of PIN 1, 15% of cases of PIN 2, and 56% of cases of PIN 3. The amount of disruption of the basal cell layer also increased with increasing grades of PIN, with loss of more than one third of the basal layer in 52% of foci of PIN 3 compared with less than 2% in lower grades of PIN. Disruption of the basal layer was more common in acini adjacent to invasive carcinoma than in distant acini. These findings suggest that early invasion in prostate cancer is characterized by disruption of the basal layer, and that invasion occurs commonly in association with foci of high-grade prostatic intra-epithelial neoplasia.
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PMID:Prostatic intra-epithelial neoplasia and early invasion in prostate cancer. 243 20

Several localized non-malignant and dysplastic glandular proliferations of the prostate mimick well-differentiated invasive prostatic microcarcinoma (PMC). However, the basal cell layer (BCL) is intact and evident in benign hyperplasias and lacking in PMC; consequently, immunohistochemical reactions for BCL, by means of keratin 903 antibody, are essential for distinguishing PMC from cribriform clear cell hyperplasia (CCCH), typical tubular hyperplasia and tubular transitional metaplasia, tubular, microtubular and cribriform basal cell hyperplasias, post-undeveloped prepuberal (PUPPUH), florid (FH) and mesonephric remnant hyperplasias. Moreover, the hyperplastic basal cells are also immunostained for prostatic specific antigen (PSA). The identification of myoepithelial cells (positive for keratin 903, actin and S100 protein antibodies) allow the diagnosis of prostatic sclerosing adenosis. Basement membrane (BM) and BCL are focally absent in post-atrophic hyperplasia (PAH), PUPPUH, FH and in extratubulo-alveolar gemmations of dysplasic lesions such as prostatic intraepithelial neoplasia (PIN), adenomatous atypical hyperplasia (AAH) and adenosis, where hypercromatic nuclei and enlarged nucleoli are the most important cytological criteria for defining malignant changes. Two putative oncogenic stages have been identified in the present work on these morphological grounds by critically examining the histogenetic hypoteses given in the literature on PMC precursors. The first is characterized by precancerous conditions such as PAH, PUPPUH, CCCH and FH that may become dysplastic though not necessarily; the second includes precancerous lesions, namely atypical tubulo-alveolar budding-in or budding-off as PIN and AAH, respectively, that may evolve towards PMC. The histogenesis of rare prostatic carcinomas are also considered. Basal cell and adenoid-cyst carcinomas seem to originate from atypical basal cell proliferations and metaplastic (transitional, adenosquamous, mucinous) carcinomas from basal and columnar-cells. Transitional and endometrioid carcinomas affect the mesonephric part of the prostate. Prostatic endocrine cells may give rise to carcinoid tumors, whereas some well-differentiated or anaplastic carcinomas may present more or less numerous endocrine cells and/or Paneth-like cells by means of a prosoplastic and ketaplastic process from neoplastic elements that underwent a stem cell backward differentiation.
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PMID:A theoretical rationale on the histogenesis of premalignant lesions and early carcinoma of the prostate. 752 11

Clusters of atrophic prostatic acini that display proliferative epithelial changes are referred to as postatrophic hyperplasia (PAH). PAH is histologically similar to adenocarcinoma and may cause diagnostic confusion. Despite the importance of distinguishing PAH from carcinoma, the last systematic study of this lesion was reported > 40 years ago, and many contemporary pathologists are unfamiliar with this lesion. We reviewed 100 consecutive whole-mount radical prostatectomy specimens removed for carcinoma to determine the incidence of PAH. In addition, 11 prostatic needle biopsy specimens with PAH were evaluated to further characterize the lesion in limited specimens. PAH was identified in 18 radical prostatectomies (18%), including 10 unicentric and eight multicentric cases. It was found exclusively in the peripheral zone in all but two cases, which had additional involvement of the transition zone. PAH consisted of a microscopic lobular cluster of small acini with irregular atrophic-appearing contours lined by cuboidal cells with mild nucleomegaly and micronucleoli; mildly enlarged nucleoli were focally present in 39% of cases. Within the small acinar cluster, a larger dilated acinus was usually present centrally, which was lined by flattened to cuboidal epithelial cells. The basal cell layer at the periphery of each acinus was invariably present but often inconspicuous. Immunohistochemical staining for high-molecular-weight keratin (antibody 34 beta E12) showed the presence of an intact basal cell layer in seven of 10 cases and a focally fragmented basal cell layer in three other cases. PAH was associated with patchy chronic inflammation in 16 of 18 prostatectomy cases; stromal changes were present in all cases, ranging from smooth atrophy to dense sclerosis with compression of acini. No intraluminal basophilic mucin was identified, but two needle biopsies showed PAH with focal mucinous metaplasia. Crystalloids were not seen in any case. Focal partial acinar involvement by high-grade prostatic intraepithelial neoplasia was present in adjacent acini in two cases. Adjacent acini also invariably showed typical changes of atrophy. In the needle biopsy specimens, PAH showed the same features as those in prostatectomies, but often only a portion of the lesion was sampled. PAH is distinguished from carcinoma by its characteristic architecture, intact or fragmented basal cell layer, inconspicuous or mildly enlarged nucleoli, and adjacent acinar atrophy with stromal fibrosis or smooth muscle atrophy. Distinguishing PAH from carcinoma is most difficult in needle biopsy specimens in which only a portion of the lesion is sampled, and awareness of this entity assists in this distinction.
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PMID:Postatrophic hyperplasia of the prostate. A histologic mimic of prostatic adenocarcinoma. 754 58

The aim of this paper is to report on a fully automated procedure to quantify the epithelial cell components in prostatic intraepithelial neoplasia with particular emphasis on the basal cell layer (BCL). Scene segmentation was guided by a knowledge-based system of digitized images recorded from histological section immunostained against high molecular weight keratin and counterstained with hematoxylin and eosin. Scene segmentation involved two major stages. First, the system located and identified the duct and segmented the scene, resulting in "intermediate segmentation products." This stage was followed by a reconstruction process in which the segmentation products (i.e., the lumen and the darkly and lightly stained epithelial cell components) were assembled to form the microscopic structure to achieve working unity. Following this, histometric measurements were made of the reconstructed scene. Computed were the percentage of the duct contour with BCL (90%), and the number and length of gaps in the BCL (19, ranging from 10 to 90 microns). Automated analysis of the BCL is accurate and provides information not readily identified by human examination.
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PMID:Prostatic intraepithelial neoplasia. Quantitation of the basal cell layer with machine vision system. 860 74

Analysis of growth factors and receptors in putative premalignant lesions of prostatic adenocarcinoma should aid our understanding of their growth pathways. Sixty prostatic TURP (transurethral resection of the prostate) specimens exhibiting atypical adenomatous hyperplasia (AAH) and/or prostatic intraepithelial neoplasia (PIN) lesions were assayed by immunohistochemistry for androgen receptor (AR), epidermal growth factor receptor (EGFR), c-erbB-2, transforming growth factor-alpha (TGF-alpha), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), MIB-1, E-cadherin, and high molecular weight keratin. Expression of these factors in the lesions was compared with that in the co-existing benign prostatic hyperplasia (BPH) or prostatic adenocarcinoma. Strong AR nuclear staining was observed in the luminal cells, but not the basal cells, of BPH and PIN lesions and in all the carcinomas examined. A similar growth factor and receptor profile was demonstrated in the secretory epithelium of high-grade PIN and carcinoma with a tendency to higher expression of membranous EGFR and c-erbB-2 and cytoplasmic TGF-alpha, and lower levels of FGF-2 than in low-grade PIN or BPH glands. Also, increased rates of proliferation, as estimated by MIB-1 stained cells, were observed in high-grade PIN in comparison with low-grade PIN and BPH and were not confined to the basal layer. AAH lesions resembled neither BPH nor carcinoma. Proliferation was virtually absent (MIB-1 expression); both AR and E-cadherin expression was significantly reduced; and, with the exception of FGF-2, all the other growth factors and receptors studied were absent. The results presented would support a premalignant role for high-grade PIN, whilst AAH would appear to represent a quiescent phenotype unlikely to progress to neoplasia.
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PMID:Expression of androgen receptor and growth factors in premalignant lesions of the prostate. 992 33

Prostatic ductal (endometrioid) adenocarcinoma has been considered a distinct pathologic and clinical entity since it was first described more than 30 years ago. Its current status as a unique neoplasm is controversial, however, because it has considerable histologic overlap with typical acinar adenocarcinoma, particularly in small specimens such as needle biopsies. There are also conflicting views regarding its clinical behavior. We recently encountered a series of typical peripheral zone cancers of the prostate gland with prominent papillary or cribriform pattern that apparently did not involve the large periurethral prostatic ducts or verumontanum. To determine the incidence of these "ductal features" in nonductal carcinoma, we reviewed the findings in 338 consecutive totally embedded whole-mount prostatectomy specimens with typical clinical and pathologic features of acinar carcinoma. We defined carcinoma with significant "ductal features" as one that displayed papillary or cribriform pattern involving an arbitrarily defined aggregate focus at least 5 mm in diameter. Anti-keratin 34beta-E12 immunohistochemical staining for basal cells allowed exclusion of areas of papillary or cribriform pattern of high-grade prostatic intraepithelial neoplasia. We identified carcinoma with ductal features (papillary or cribriform growth) in 17 prostatectomy specimens (5% of cases) exclusively in the peripheral zone without involving the periurethral region. Papillary pattern was present in 11 of these cases (65%) and cribriform pattern in 10 (59%), including 4 cases (24%) with both patterns. Of 11 needle biopsy specimens available for examination from these 17 cases, 4 (36%) contained at least focal papillary or cribriform pattern of carcinoma. We conclude that adenocarcinoma arising in the peripheral zone of the prostate gland may display ductal carcinoma features (papillary or cribriform growth) classically associated with ductal adenocarcinoma. These findings, together with the recognized near-constant association of prostatic ductal adenocarcinoma and typical prostate cancer, suggest that ductal adenocarcinoma results from spread of typical prostatic acinar carcinoma into the large accommodating periurethral ducts and stroma, and that there are no unique histologic features other than site of growth. Identification of papillary or cribriform growth of cancer in prostate needle biopsies usually results from peripheral zone adenocarcinoma and not ductal adenocarcinoma.
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PMID:Does prostatic ductal adenocarcinoma exist? 1040

Prostatic adenocarcinoma resembling benign hyperplastic glands architecturally is a recently recognized entity. In the only prior study on this entity, 100 needle biopsies were studied and only two contained carcinoma with pseudohyperplastic features, which occupied a small percentage of the cancer. The current study investigates histologic attributes of pseudohyperplastic prostatic adenocarcinoma on needle biopsy and simple prostatectomy in which the pseudohyperplastic regions represent the majority of the cancer. The authors reviewed outside cases received in consultation by one of the authors (J.I.E.) and the surgical pathology files of Johns Hopkins Hospital from January 1991 to August 1998 and identified 20 cases of needle biopsy and simple prostatectomy in which > or =60% of the cancer had benign architectural features. The majority (19 of 20) were consult cases. Of the 20 cases studied, 16 were needle biopsies, two were transurethral resections of the prostate, and two were enucleations. Cancer involved one core in 75% of the needle biopsies. In 13 of the 20 cases (65%), > or =90% of the cancer had pseudohyperplastic features. Benign features included papillary infoldings in all cases, large atypical glands in 95% of cases, branching in 45% of cases, and corpora amylacea in 20% of cases. The extent of pseudohyperplastic cancer ranged from 1.0 to 10.0 mm (average, 3.7 mm). Within the pseudohyperplastic foci, features helpful in establishing a malignant diagnosis were nuclear enlargement in 95% of cases, pink amorphous secretions in 70% of cases, occasional to frequent nucleoli in 45% of cases, and crystalloids in 45% of cases. Other features associated with malignancy (mitoses, blue-tinged mucin, adjacent high-grade prostatic intraepithelial neoplasia, and perineural invasion) were seen infrequently. Immunohistochemical stains for high-molecular weight keratin showed an absence of basal cells in the pseudohyperplastic areas in all 20 cases, confirming the diagnosis of cancer. It is critical to recognize pseudohyperplastic prostatic adenocarcinoma and the features needed to establish a malignant diagnosis so these carcinomas are not misdiagnosed as benign.
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PMID:Pseudohyperplastic prostatic adenocarcinoma on needle biopsy and simple prostatectomy. 1093 44

Alpha-methylacyl coenzyme A racemase (AMACR) is a recently discovered enzyme protein that has been shown to be increased at both the mRNA and protein levels in prostatic adenocarcinoma as compared with normal prostatic tissues. Since its discovery, AMACR has gained wide acceptance for use in the diagnosis of prostatic adenocarcinoma in conjunction with morphology and immunohistochemical staining for basal cell markers. Numerous studies have consistently shown high sensitivity and specificity of AMACR for prostate cancer. This review focuses on AMACR expression in prostate cancer and its morphologic variants, high grade prostatic intraepithelial neoplasia, adenosis and benign conditions of the prostate. In addition, we discuss AMACR expression in other tumors. We also focus on the utility and technical aspects of the now-popular "triple stain" immunohistochemical antibody cocktail, consisting of antibodies to high-molecular-weight keratin, p63 and AMACR. Finally, we emphasize diagnostic pitfalls in the application of AMACR to small, atypical foci of glands seen on prostate needle core biopsy and project future diagnostic as well as clinical applications for the protein.
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PMID:Application of alpha-methylacyl coenzyme A racemase immunohistochemistry in the diagnosis of prostate cancer: a review. 1656 75