Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oncocytic neoplasms of the adrenal gland are rare. We describe the clinicopathologic and immunohistochemical findings of seven oncocytic adrenocortical neoplasms, five oncocytomas, and two oncocytic neoplasms of uncertain malignant potential. Three tumors were studied using electron microscopy. These neoplasms occurred in five women and two men (median age, 55 years) with no clinical evidence that the neoplasms were functional. The size of the neoplasms varied from 5.0 cm to 13.5 cm. Histologically, each neoplasm was composed exclusively of oncocytes. The oncocytomas had very low or absent mitotic activity and no evidence of necrosis. The two oncocytic neoplasms of uncertain malignant potential had increased mitotic activity and necrosis but no evidence of invasion or metastases. Nuclear atypia, either focal or generalized, was found in all neoplasms. Immunohistochemical studies performed using fixed, paraffin-embedded sections showed strong reactivity with the mitochondrial antibody mES-13 in all neoplasms. Four of five oncocytomas and one oncocytic neoplasm of uncertain malignant potential expressed keratin, predominantly keratin 18, as shown using the CAM 5.2 and AE3 antibodies. Two neuroendocrine-associated markers, neuron specific enolase and synaptophysin, were positive in seven and five neoplasms, respectively. However, all neoplasms were negative for the other neuroendocrine markers tested, including chromogranin A, tyrosine hydroxylase, and dopamine beta-hydroxylase, as well as for epithelial membrane antigen, S100, and p53. Using the MIB-1 (Ki-67) antibody, proliferative activity was increased in both oncocytic neoplasms of uncertain malignant potential. All six patients with available clinical follow-up data are alive without evidence disease, although the follow-up interval is relatively short (< 2 years) for the two patients with oncocytic neoplasms of uncertain malignant potential. We conclude that oncocytic adrenocortical neoplasms are nonfunctional tumors that can become large before they are detected by radiologic studies. The majority of neoplasms are benign and should not be misdiagnosed as carcinoma.
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PMID:Oncocytic adrenocortical neoplasms: a report of seven cases and review of the literature. 959 31

A cohort of 109 patients with primary transitional cell carcinomas, stages T2-T3, grade 2 or higher, was identified and further divided into two groups based on lymphatic metastasis at the time of cystectomy (n = 57 cases) or absence of detectable metastatic disease over a minimum of 5 years of follow-up after cystectomy (n = 52). Blocks corresponding to the primary tumor lesions were sectioned and distributed to different laboratories to be analyzed. Immunohistochemistry on deparaffinized tissue sections was conducted for evaluation of p53 nuclear overexpression (monoclonal antibody PAb1801), assessment of proliferative index (Ki-67 antigen-monoclonal antibody MIB1), and microvascular counts (factor VIII-related antigen). DNA content/ploidy studies were performed on material obtained from thick sections. A double-blinded strategy was used for the evaluation of laboratory data versus clinical parameters. The cutoff value for p53 nuclear overexpression was > or =20% of tumor cells displaying nuclear staining. The median values for MIB1 (> or =18% of tumor nuclear cell staining) and microvascular counts (> or =40 microvessels/area screened) were used as cutoff points for these two variables. The assessment of DNA content was conducted by classifying cases as diploid, tetraploid, or aneuploid. Statistical analyses were performed using the Fisher's Exact Test (2-tailed). Results revealed that none of the markers studied had a statistically significant correlation with the end point of the study, i.e., the presence of lymph node metastatic disease, in the cohort of patients studied, although an obvious trend for p53 was noted. It is concluded that alterations of p53, Ki-67 proliferative index, microvascular counts, and ploidy are not strongly associated with lymph node status in patients affected with high-stage, high-grade bladder cancer.
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PMID:Biomarker study of primary nonmetastatic versus metastatic invasive bladder cancer. National Cancer Institute Bladder Tumor Marker Network. 960 86

Gastrointestinal stromal tumors (GIST) constitue the largest category of primary non-epithelial neoplasms of the stomach and small bowel. They are characterized by a remarkable cellular variability and their malignant potential is sometimes difficult to predict. Very recent studies, using mitotic count and tumor size as the best determinants of biological behavior, divide GISTs into three groups: benign, borderline and malignant tumors. We report on a male patient who underwent a right hepatectomy for a large metastasis 11 years after the surgical treatment of an antral-pyloric gastric neoplasm, histologically defined as leiomyoblastoma and with clinical, morphological and immunohistochemical features of benignity (low mitotic count, tumor size < 5 cm, low cellular proliferation index). Histological and immunohistochemical analysis of the hepatic metastasis showed the cellular proliferation index (Ki-67) to be positive in 25% of neoplastic cells, as opposed to the primary gastric tumor in which Ki-67 was positive in only 5% of neoplastic cells. In conclusion, although modern immunohistochemical techniques are now available to obtain useful prognostic information, the malignant potential of GISTs is sometimes difficult to predict: neoplasms clinically and histologically defined as benign could metastasize a long time after oncologically correct surgical treatment. Therefore, benign GISTs also require consistent, long-term follow-up.
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PMID:Gastrointestinal stromal tumors: a "benign" tumor with hepatic metastasis after 11 years. 961 21

Four unusual cases of primary mammary mucinous cystadenocarcinoma composed predominantly of tall columnar cells with abundant intracytoplasmic mucin are reported; they were multicystic and appeared virtually identical to mucinous cystadenocarcinomas of the ovary and pancreas. Three of the women were white and one was black, they ranged in age from 49 to 67 years (average 58), and they had tumors that ranged from 0.8 to 19 cm in diameter. Microscopically, the tumors were characterized by cystic spaces lined by predominantly bland-appearing columnar mucinous cells with stratification, tufting, and papillary formations. Varying degrees of cytologic atypia were focally evident, with gradual loss of the intracytoplasmic mucin and transformation to an eosinophilic squamoid cell population. Multifocal invasion generally emanated from these eosinophilic, squamoid areas in all cases. All four tumors displayed immunoreactivity for MIB-1 (Ki-67) in a relatively high percentage of cells and failed to show immunoreactivity for estrogen receptors and progesterone receptors. All four stained positively with cytokeratin 7 (CK7) but were negative with cytokeratin 20 (CK20). Mastectomy and axillary lymph node dissection were performed in three cases and lumpectomy with lymph node dissection in the remaining case. Lymph node metastases, identified in only one patient, retained the distinctive morphology. Three of the patients are alive without evidence of disease 11, 22, and 24 months after the diagnosis; the fourth is a recent case. These tumors are a rare, clinicopathologically distinct type of primary breast carcinoma that should be distinguished from typical mucinous (colloid) carcinomas of the breast and, more importantly, metastases from other sites.
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PMID:Mucinous cystadenocarcinoma of the breast. 963 Jan 76

Biopsy specimens from 12 patients with metastatic melanoma were longitudinally analysed to evaluate changes in proliferation activity and CD4+/CD8+ ratios during the course of the disease. The primary tumours of the patients who subsequently had metastatic disease were also each matched with tumours from two controls whose disease remained localized, and were compared with regard to tumour proliferation. Immunohistochemistry was performed using the avidin-biotin complex (ABC) immunoperoxidase technique, using bcl-2, p53, mdm-2 and Ki-67 as the primary monoclonal antibodies, and the percentage of positively stained melanocytic cells was calculated. Frozen sections were also available from metastatic lesions excised from eight of our patients before treatment initiation and at the time of disease progression. These specimens were prepared for microscopy, and quantitative characterization of CD4+ (OKT 4a) and CD8+ (OKT 8) cells was performed. Compared with the localized melanomas bcl-2 expression was higher in those primary melanomas that later metastasized (P = 0.068, Wilcoxon; P = 0.038, median test). Mdm-2 and Ki-67 expression did not differ in the primary tumours of patients and controls, but a statistically significant trend was observed towards increasing expression with the progression of the disease (two-sided exact P-values: 0.04 and 0.05, respectively). Patients with a low Ki-67 index in their first metastasis had a better prognosis when compared with patients with high indexes (P = 0.008, log-rank). Furthermore, most patients with decreasing CD4+/CD8+ ratios had increasing p53 immunoreactivity. Our findings suggest that Ki-67 and bcl-2 may be useful for predicting the prognosis of melanoma patients. Mdm-2 is a new but promising marker in melanoma and deserves further evaluation.
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PMID:Prognostic value of biomarkers in malignant melanoma. 966 52

Carbonic anhydrase isoenzyme IX, MN/CA IX, is a recently discovered member of the carbonic anhydrase (CA) gene family with a suggested function in acid-base balance, intercellular communication, and cell proliferation. Increased expression of MN/CA IX has been observed with certain epithelial tumors. We investigated the expression of MN/CA IX in 69 colorectal neoplasms, consisting of 1 juvenile polyp, 8 hyperplastic polyps, 39 adenomatous lesions, 21 carcinomas, and 7 metastases. Tissue sections were immunostained with a monoclonal antibody specific to MN/CA IX. The proliferative activity of the tumor cells was evaluated by Ki-67 antigen immunoreactivity. The hyperplastic polyps showed a weak or moderate reaction for MN/CA IX only in the cryptal epithelium, as did the normal intestinal mucosa. The adenomas showed immunoreactivity mainly in the superficial part of the mucosa, whereas the distribution in the carcinomas and metastases was more diffuse. Comparative immunostaining of serial sections for Ki-67, a well established marker of cell proliferation, confirmed that MN/CA IX is expressed in areas with high proliferative capacity. Our results show abnormal MN/CA IX expression in colorectal neoplasms, suggesting its involvement in their pathogenesis. The co-occurrence of MN/CA IX and Ki-67 in the same tumor cells indicates its potential for use as a marker of increased proliferation in the colorectal mucosa.
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PMID:Immunohistochemical study of colorectal tumors for expression of a novel transmembrane carbonic anhydrase, MN/CA IX, with potential value as a marker of cell proliferation. 966 57

The rates of proliferation, determined on the basis of antigen Ki-67 detection, and activity of nucleolar organizer regions (AgNORs) were compared in 10 benign lesions and 48 breast cancers (mostly invasive ductal carcinomas). Antigen Ki-67 was detected by the indirect immunoperoxidase method using polyclonal rabbit antibodies. Proteins of AgNORs were silver-stained after W.M. Howell and D.A. Black (modified by N.N.Mamayev). The fraction of Ki-67-positive cells--very close to proliferative pool--was 4.75 (1.60-11.76)% in benign tumors and 24.89 (8.64-65.16)%--in breast cancer, respectively. There was a significant correlation between Ki-67 expression and degree of histologically malignancy of breast tumors. There was a high correlation between Ki-67 expression in primary tumors and their metastases to regional lymph nodes; however, in metastases, the number of Ki-67-positive cells was significantly lower than in primary tumor. Also, the study established a distinct relationship between such indices of AgNOR activity as numbers of intra- and extranucleolar granules of silver and their total number in nucleus, on the one hand, and index of cell proliferation, on the other. The former represented specific clinicoanatomical features of tumor.
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PMID:[Comparative study of the proliferation (by detection of Ki-67 antigen) and activity of nucleolar organizer regions in breast cancer cells]. 969 79

To determine the prognostic impact of clinical, immunohistochemical, and biological parameters, we examined 52 gastrointestinal stromal tumors (GIST) by conventional light microscopy and immunohistochemistry. DNA ploidy was analyzed by image cytometry on cytospin preparation. The proliferative activity was determined by mitosis counting and assessment of Ki-67 reactivity by means of monoclonal antibody Ki-S5. A histopathologic grade was assigned to each tumor according to the French Federation of Cancer Centers (FNCLCC) grading system. Next to vimentin, CD34 was the most prevalent antigen, followed by markers of neural and muscular differentiation. Many tumors exhibited a mixed phenotype. Twenty-one tumors were diploid, eight hypodiploid, and 23 aneuploid. In univariate analysis, tumor grade, Ki-S5 labeling index, mitotic count, atypical mitoses, cellularity, and sex were predictive of both mortality and metastasis risk. DNA ploidy only correlated with overall survival, whereas the tumor location affected the occurrence of metastases. Multivariate analysis selected Ki-S5 scores (P < .0001) and atypical mitoses (P=.012) as independent prognosticators for overall survival, and tumor grade (P=.0036) and size (P=.0055) as predictors of metastatic spread. We conclude that GIST are primitive mesenchymal tumors capable of divergent differentiation, which does not influence their prognosis. The latter appears to be best predicted by histopathologic grading and the Ki-67 labeling index.
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PMID:Immunophenotype, proliferation, DNA ploidy, and biological behavior of gastrointestinal stromal tumors: a multivariate clinicopathologic study. 971 19

In a retrospective case-control study on 46 metastasized and 34 non-metastasized primary tongue carcinomas, the nuclear morphology and chromatin pattern were assessed in 3 microns thick, formalin-fixed, paraffin-embedded, and Feulgen-stained tissue sections of surgical resection specimens, by means of high-resolution computer-assisted image analysis. The aim of this study was to disclose differences in karyometric features, such as nuclear size-, shape-, and chromatin-pattern features, between these groups, with a view to developing a discriminant function that can predict the occurrence of metastasis for the individual patient. In addition, the lymph node metastases of 31 patients and the normal tongue epithelium of 21 patients were also assessed, to study the possible differences between these two groups and primary tumours. In the metastasized tumours, the chromatin was significantly more condensed (P = 0.01) and exhibited significantly less variation in chromatin condensation (P < 0.001) than in the group of non-metastasized carcinomas. Comparison of lymph node metastases with their primary tumours disclosed only minor differences in chromatin pattern. These findings suggest that only minor genetic differences exist between primary tongue carcinomas and their metastases. Tumour cells of tongue carcinomas showed highly significant differences from cells of normal tongue mucosa for most karyometric features. Logistic regression analysis resulted in a classifier, based on the circularity of the nucleus (CIRC) and the standard deviation of the chromatin condensation (SD COND), to predict the occurrence of lymph node metastases. After cross-validation, the percentages of correct classifications in the group of metastasized and non-metastasized tumours were 72 and 62 per cent, respectively. These results are comparable to the classification results obtained from a classifier based on the clinical T-stage, but our karyometric classification results show a much more equal distribution between the sensitivity and specificity. Karyometric features appeared to be more appropriate to predict metastases than biomarkers such as p53, bcl-2, and Ki-67.
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PMID:An image analysis study on nuclear morphology in metastasized and non-metastasized squamous cell carcinomas of the tongue. 971 44

The cyclin-dependent kinase inhibitor p27 is a negative regulator of the cell cycle and a potential tumor suppressor gene. Because we had previously demonstrated that loss of p27 protein is associated with aggressive behavior in colorectal adenocarcinomas, we used immunohistochemistry and in situ hybridization to evaluate the potential role of alterations in p27 expression in primary and metastatic colorectal adenocarcinomas. Parallel immunostaining was performed for Ki-67 and p53. We evaluated 13 cases of metachronous and 23 cases of synchronous primary and metastatic colorectal tumor pairs. In the synchronous subgroup (Stage IV tumors), 57% of the primary tumor and metastases pairs did not express p27 protein and the remainder were low expressors. In the metachronous subgroup, 54% of the primary tumors were low expressors and the remainder high expressors of p27 protein. There was a significant reduction in the expression of p27 in the metachronous metastases (mean positive cells: 14.5%) when compared to the corresponding primary tumors (mean positive cells: 41.8%), P = 0.0023. All the primary and metastatic tumors in the metachronous subgroup showed high levels of p27 mRNA expression. There was no association between loss of p27 and either Ki-67 count or p53 expression. Because p27 is known to be up-regulated when epithelial cells are grown in suspension, the down-regulation of p27 in circulating tumor cells may confer the ability to grow in an environment of altered extracellular matrix or intercellular adhesion properties, two situations which may facilitate metastases.
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PMID:Down-regulation of p27 is associated with development of colorectal adenocarcinoma metastases. 973 17


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