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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the study of carcinogenesis most interest has focused on carcinomas, as they represent the majority of human cancers. The recognition of the adenoma-carcinoma sequence both in humans and in animal experimental models has given the field of basic oncology the opportunity to elucidate individual mechanisms in the multistep development of carcinoma. The relative scarcity of human sarcomas coupled with the lack of adequate animal models has hampered understanding of the molecular genetic steps involved. We present an experimental model in the rat in which a high incidence of malignant mesenchymal tumors arise around a subcutaneously implanted biomaterial. Nine commercially available biomaterials were implanted in a total of 490 rats of the Fischer strain for 2 years. On average, macroscopic tumors were found in 25.8% of implantation sites over a period from 26 to 110 weeks after implantation. The most frequent tumors were malignant fibrous histiocytomas and pleomorphic sarcomas, although fibrosarcomas, leiomyosarcomas, and angiosarcomas readily developed, the latter especially around polyurethane implants. Of particular interest are the results of a detailed histological study of the capsules around the implanted biomaterials without tumors. Here a spectrum of change from focal proliferative lesions through preneoplastic proliferation to incipient sarcoma could be observed. A parallel immunohistochemical study of peri-implant capsules showed that proliferating cell nuclear antigen was of particular help in identifying these atypical proliferative lesions. To our knowledge this is the first description of a sarcoma model in which preneoplastic lesions can be readily identified and also reproducibly induced. This model provides the molecular biologist with defined stages in the development of mesenchymal malignancy, with which the multistage tumorigenesis hypothesis can be tested, analogous to the well-known adenoma-carcinoma sequence.
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PMID:Biomaterial-induced sarcoma: A novel model to study preneoplastic change. 1075 69

Colorectal neoplasms obtained at colonoscopy were examined by argyrophilic nucleolar organizer region (AgNOR) staining to evaluate the usefulness of AgNOR as a discriminant for malignancy. AgNOR dots were divided into two kinds: 'structures' (larger and less-densely stained) corresponding to the nucleolus, and 'units' (smaller and densely stained) presumed to be true AgNOR within the structure. The number of structures per nucleus did not differ between the adenoma and carcinoma groups, whereas the number of units per nucleus showed a significant difference. However there were several cases showing an overlap between the adenoma and carcinoma groups, leading to a difficulty in deciding whether any given case was benign or malignant. Three types of AgNOR patterns were categorized based on the ratio of units to structure. Type I was defined as the unit being indistinguishable from the structure, Type II as each structure having one to five units, and Type III as at least one structure having six or more units, irrespective of total number of units per nucleus. The colorectal lesions in which more than half of the neoplastic cells showed Type III coincided well with carcinomas histologically diagnosed, with the exception of adenomas with severe atypia. Labeling index of proliferating cell nuclear antigen (PCNA LI) differed between the adenoma and carcinoma groups with a considerable extent of overlap, and correlated to some extent with the AgNOR values. These results showed that the AgNOR staining was useful for determining malignancy and its usefulness appeared superior to PCNA LI.
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PMID:Argyrophilic nucleolar organizer regions in colorectal malignancy: application of typing by their density. 1084 71

Although rectal mucosal labeling index is thought to be a useful surrogate biomarker for colorectal cancer, the ability of the index to predict future neoplasia is unclear. We obtained rectal mucosal biopsies from 333 participants of a randomized controlled chemoprevention trial of calcium supplementation to determine whether labeling index was correlated with concurrent or future colorectal neoplasms. Labeling index was measured using proliferating cell nuclear antigen immunohistochemistry. Adenomas were enumerated at the time of the biopsies (cross-sectional) and 3 years later (prospective). We used logistic regression to test for an association of adenoma occurrence with overall labeling index, the mean proliferative height, and labeling index in the upper 40% of colon crypts. In the cross-sectional analysis, we found indications that higher proliferation was associated with an increase in the prevalence of adenomas. The overall adjusted odds ratios (OR) (95% confidence interval) were 1.14 (0.90-1.45) per % crypt labeling index, OR 1.08 (0.99-1.19) for upper crypt proliferation, and OR 1.07 (1.03-1.12) for proliferative height. In contrast, individuals with higher labeling index at baseline were actually less likely to have adenomas in the prospective analyses: OR 0.80 (0.62-1.02) per % crypt labeling index, OR 0.86 (0.73-1.00) for upper crypt index, and OR 0.97 (0.93-1.01) for proliferative height. Proliferative index does not predict future colorectal neoplasia, although it may be weakly associated with the presence of current adenomas. These results have important implications for the design of future intervention studies. Although it may be attractive to include the measurement of intermediate markers in large controlled trials, until we have more confidence in their performance, we should rely on better proven and more reliable intermediates, such as adenomas.
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PMID:Rectal mucosal proliferation and risk of colorectal adenomas: results from a randomized controlled trial. 1091 33

Immunostaining for bcl-2 protein was performed in 27 colorectal adenomas and 108 colorectal adenocarcinomas. The aim of the study was to determine bcl-2 expression in correlation with p53, mdm-2 and Rb expression, with proliferation indices (Ki-67-LI, PCNA-LI) as well as with conventional clinicopathological variables. A higher proportion of adenomas (30.8%) than carcinomas (16.7%) expressed bcl-2 and conversely, a lower proportion of adenomas (7.4%) than carcinomas expressed p53 (57.1%), the difference being statistically significant (p<0.0001). No correlation of bcl-2 expression with p53 expression (parallel or inverse) as well as with the other parameters studied was observed in any tumour. The bcl-2+/p53- subgroup of cancers showed a trend for correlation with negative lymph node status. Our data suggest, that bcl-2 expression may be involved in the early phase of colorectal carcinogenesis regardless of p53 status, while p53 function may be involved in a late stage of the adenoma-carcinoma sequence. P53 is apparently not involved in the regulation of apoptosis in the colorectal neoplasias or perhaps bcl-2 expression, as an early event in colorectal tumours, may occur before changes of p53 take place. Tumours with bcl-2+/p53- immunophenotype are frequently associated with negative lymph node status and seem to have a less aggressive behavior.
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PMID:Bcl-2 expression in colorectal tumours. Correlation with p53, mdm-2, Rb proteins and proliferation indices. 1096 9

A case of epithelial-myoepithelial carcinoma (EMC) in pleomorphic adenoma (PA) occurring in the palate of a 72-year-old woman is reported. The tumor was composed of 2 different components, PA and EMC, accounting for approximately 40% and 60% of the whole tumor, respectively. The EMC showed multiple tubular or solid nests, which were separated by a basement membrane and consisted of variable proportions of 2 cell types, cuboidal epithelial cells positive for cytokeratin and clear myoepithelial cells positive for glial fibrillary acid protein, whereas the myoepithelial nests of PA intermingled with hyaline and myxoid stroma. The malignancy was demonstrated by convincing evidence of invasion into the submucosa, although the EMC component was mostly surrounded by the PA components. An increased immunoreactivity of proliferating cell nuclear antigen in the EMC area in comparison to the PA area also suggested EMC arising in a PA.
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PMID:Epithelial-myoepithelial carcinoma arising in pleomorphic adenoma of the palate. 1102 83

Cell proliferation rate and apoptosis were examined in archival kidneys from young, middle-aged, and old male F344 rats. Immunohistochemical expression of proliferating cell nuclear antigen (PCNA) and apoptosis were quantified in the same cell populations of the proximal tubule epithelium. A total of 79 kidneys from 40 rats were examined. There was a progressive increase in cell proliferation rates in rats from 4 and 6-10 months of age. In 23-month-old rats, proliferative activity appeared to be reduced. No age-related variations in apoptotic indices were found. One of the 16 rats aged 23 months had a tubular cell adenoma. In the tumor-affected kidney, cell proliferation rate was dramatically higher than in the contralateral kidney as well as in all the other kidneys examined. This high proliferative activity was not balanced by variation in cell death.
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PMID:Age-related cell proliferation and apoptosis in the kidney of male Fischer 344 rats with observations on a spontaneous tubular cell adenoma. 1112 94

The frequency of point mutations in p53 (exons 4-7) and in Ki-ras, Ha-ras, and N-ras (exons 1 and 2) and the expression of p53 protein were evaluated in the liver tumors of Wistar rats of a 104-week carcinogenicity study on 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a chlorine disinfection by-product in drinking water. Mutations were analyzed in 16 hepatocellular adenomas, 7 hepatocellular carcinomas, 23 cholangiomas, and 2 cholangiocarcinomas of the MX-treated animals and one hepatocellular carcinoma and cholangiocarcinoma in control animals using PCR-SSCP (polymerase chain reaction-single-strand conformation polymorphism) or PCR-TGGE (temperature gradient gel electrophoresis) and direct sequencing. The expression of the p53 protein (wild-type and mutated protein) was detected by immunohistochemistry (CM5 antibody). The expression of p53 and that of the proliferating cell nuclear antigen (PCNA, 19 A2) were also evaluated in livers of female animals exposed to MX for 1 week, 3 weeks, or 18 weeks. Altogether, four mutations were found in p53 in three tumors, in two hepatocellular adenomas, and one cholangiocarcinoma, all in females receiving the highest MX dose (6. 6 mg/kg/day) of the study. Three of the mutations were G:C --> A:T transitions and one was an A:T --> T:A transversion. The mutations were scattered at different codons and positions of the codon. One hepatocellular adenoma contained two p53 mutations. All cholangiomas and cholangiocarcinomas, but no hepatocellular adenomas and carcinomas, overexpressed the p53 protein. MX treatment did not induce p53 expression at any age in the liver or alter the expression of the PCNA in the liver of younger animals. The p53 protein was overexpressed in hyperplastic bile ducts in aged rats but not in bile ducts of younger rats (up to 24 weeks). No mutations were observed in either Ki-ras, Ha-ras, or N-ras of the liver tumors. These data suggest that point mutations in p53, Ki-ras, Ha-ras, and N-ras are not involved in the MX-induced liver carcinogenesis in rats.
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PMID:No consistent pattern of mutations in p53 and ras genes in liver tumors of rat treated with the drinking water mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX). 1115 62

'de novo' carcinogenesis has been advocated besides 'adenoma carcinoma sequence' as another dominant pathway leading to colorectal carcinoma. Our recent study has demonstrated that the distribution of brain (fetal)-type glycogen phosphorylase (BGP) positive foci (BGP foci) has a close relationship with the location of 'de novo' carcinoma. The aims of the present study are to investigate genetic alteration in the BGP foci and to characterize them in the 'de novo' carcinogenesis. 17 colorectal carcinomas without any adenoma component expressing both immunoreactive p53 and BGP protein were selected from 96 resected specimens from our previous study. Further investigations to examine the proliferating cell nuclear antigen (PCNA)-labelling index, and the p53 and the codon 12 of K-ras mutation using the polymerase chain reaction-single strand conformation polymorphism were performed in the BGP foci, BGP negative mucosa and carcinoma. The BGP foci were observed sporadically in the transitional mucosa adjacent to the carcinoma in all cases. The PCNA labelling index in the BGP foci was significantly higher than that in the BGP negative mucosa (P< 0.001). p53 mutations were observed in 8 carcinomas, but no K-ras mutation was detected. Interestingly, although none of the overexpressions of p53 protein was detected immunohistochemically in the BGP positive foci, the p53 gene frequently (41.2% of the BGP foci tested) mutated in spite of no K-ras mutation. The present study demonstrates potentially premalignant foci in the colorectal transitional mucosa with frequent p53 gene mutation. It is suggested that BGP foci are promising candidates for the further investigation of 'de novo' colorectal carcinogenesis.
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PMID:Frequent p53 mutation in brain (fetal)-type glycogen phosphorylase positive foci adjacent to human 'de novo' colorectal carcinomas. 1138

The oncogenes cyclin D1 and D3 are overexpressed in many tumors. Topoisomerase II alpha is found in proliferating cells. The immunohistological expression of cyclin D1, cyclin D3, and Topoisomerase II alpha was studied in a collection of 60 clinically inactive surgically removed pituitary adenomas of the follicle-stimulating hormone/luteinizing hormone (FSH/LH) cell complex (20 null cell adenomas, 20 oncocytomas, and 20 FSH/LH cell adenomas) for correlation with other proliferation markers (Ki-67, PCNA) and with clinical data. Whereas cyclin D1 was positive only in one invasive null cell adenoma (1.7%) with some p53-positive nuclei, cyclin D3 was overexpressed in the nuclei of 41 tumors (68%). Topoisomerase II alpha was demonstrated in the nuclei of 42 adenomas (70%) with no significant differences discernible between the three adenoma subtypes. There was no significant correlation to the time of development of tumor symptoms, but a correlation of Topoisomerase II alpha with cyclin D3 and the proliferation marker Ki-67 (Mib1). From these data we conclude that cyclin D3 and Topoisomerase II alpha appear to be additional markers for proliferation which can be used for prognosis index in surgical pathology of the pituitary.
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PMID:Cyclins D1 and D3 and topoisomerase II alpha in inactive pituitary adenomas. 1147 67

This report describes an illustrative case of adenomatoid hyperplasia (AH) of the minor salivary glands on the palate of a 31-year-old man. The clinical features of the present lesion corresponded with those of pleomorphic adenoma, but histologically large lobules of normal-appearing mucous acini were found. The cell proliferative activity demonstrated in histological sections, by an immunohistochemical staining of proliferating cell nuclear antigen and Ki-67, showed no statistically significant differences among AH and a matched control group of normal palatal salivary glands. This case suggests that AH apparently exhibits an idiopathic, focal hypertrophic lesion of intraoral mucous glands with limited growth potential.
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PMID:Adenomatoid hyperplasia of the palate mimicking clinically as a salivary gland tumor. 1151 98


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