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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular genetic alterations in colorectal carcinoma are among the best understood of any common human cancer. Identified abnormalities include both dominant-acting oncogenes (ras, myc, src) and suppressor genes which undergo inactivation or deletion (deleted in colorectal carcinoma gene [DCC], p53, adenomatous polyposis coli gene [APC], and probably loci on chromosomes 1p and 22q). Accumulation of multiple abnormalities is evident in the adenoma-carcinoma sequence with a preferential order, and alteration of DNA methylation is an especially early event. Identification of molecular genetic markers useful for classification and staging of colorectal carcinoma is in its infancy. Deletion of the p53 gene on chromosome 17p, deletion of the DCC gene on 18q, and high fractional allelic loss (fraction of evaluable nonacrocentric autosomal arms with deletion) have been associated with distant metastases and with poorer prognosis in patients without initial evidence of disseminated disease. Additional studies are needed to determine the possible role of these alterations in clinical management.
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PMID:Molecular genetic alterations as potential prognostic indicators in colorectal carcinoma. 154 Sep

Cell adhesion molecules (CAMs) of the immunoglobulin supergene family may play important roles in tumorigenesis and the development of metastatic disease. In a variety of human malignancies, tumor progression has been observed to be associated with changes in CAM expression. An early event in colorectal tumorigenesis appears to be the down regulation of a normally expressed CAM, DCC. Over-expression of a second CAM, carcinoembryonic antigen, is associated with colorectal tumors which have a high risk for metastasis development. Several tumors, including Wilms tumors and neuroblastoma, have been found to express a developmentally regulated form of NCAM which inhibits a variety of cell-cell interactions. Malignant cells not only show aberrations in the expression of their CAMS and thus their normal cell-cell interactions, but establish new adhesive interactions. The development of metastatic potential in cutaneous melanoma is associated with the de novo expression of two CAMs, one of which is ICAM-1, a molecule mediating adhesion between the tumor cells and leukocytes.
Cancer Metastasis Rev 1991 May
PMID:Cell adhesion molecules of the immunoglobulin supergene family and their role in malignant transformation and progression to metastatic disease. 168 May 75

Inactivation of tumor suppressor genes is now believed to play an important role in various progression stages of human cancers. To clarify the possible involvement of tumor suppressor gene inactivation in the acquisition of metastatic potential in lung and colorectal carcinoma cells, we examined various genetic alterations in both primary tumors and metastases obtained from patients with lung and colorectal carcinomas. In lung carcinoma, loss of heterozygosity on chromosomes 3p, 13q, and 17p is a common genetic alteration, and both RB and p53 genes are inactivated as a result of chromosome 13q and 17p losses. In some cases, allelic loss on chromosome 11p and amplification of myc family oncogenes occur during tumor progression. In colorectal carcinoma, p53 and DCC alterations were detected in 100% of metastases, and sequential accumulation of allelic losses on chromosomes 13q, 14q, and 18q in the process of metastasis was observed. These results indicate that a subset of tumor suppressor genes is involved in metastasis of lung and colorectal carcinomas.
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PMID:Tumor suppressor genes involved in metastasis of lung and colorectal carcinomas. 184 53

The biochemical analysis of estrogen receptor (ER) content, using the DCC (dextran-coated charcoal) method, was compared with different plotting methods of the estrogen-receptor immunocytochemical assay (ER-ICA) in 80 primary breast cancers including 9 metastases under routine conditions. It was evident, that the determined content of estrogen receptors depends on the technique of measurement, as well as the microscopic organizations of the individual carcinomas and should be interpreted in respect of their content of stroma and if possible of tumour heterogeneity.
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PMID:[Interpretation of the estrogen receptor content of breast cancer]. 235 83

Estrogen receptor (ER) immunocytochemical assay (ER-ICA) was assessed human breast carcinomas. The patient's age, the tumor size, the histological type and SBR grade, the presence or the absence of axillary lymph node metastases and of vessel invasion in tumor borders were recorded in all the cases included in the series (n = 469) estrogen and progesterone receptors were concomitantly evaluated (DCC method) and or immunoenzymatic assays. Monoclonal H222 sp gamma and PAP procedure (Abbott kit) were applied in frozen sections, tumor imprints and fine needle aspirates. A computerized system of image analysis referred to as SAMBA (TITN), permitted to achieve a multiparametric quantitative analysis of ER positive surfaces. With this system, in each tumor, the cellularity, the percentage ER surface versus the total cell surface and versus the epithelial (keratin positive) surface, integrated optical density (IOD), mean optical density, index of the concentration of labelled objects, and IOD histograms, were obtained and correlated to histological and biochemical data. It was shown that: 1) ER antigenic sites were heterogeneously distributed in ER positive tumors, with a specific nuclear localization in epithelial cells; 2) the SAMBA 200 multiparametric analysis of the ER sites distribution in tissue was appropriate, accurate, reproductible and therefore more reliable than the semi-quantitative analysis; 3) the standardization and the complete automation of this method of immunoprecipitates evaluation on tissue section permit to daily and to routinely analyse a large number of preparation; 4) there was a correlation between ER binding sites evaluation (DCC) and ER antigenic sites immunodetection (ER-ICA and ER-EIA); 5) there was a correlation between the SAMBA evaluation of ER-ICA and other histological prognostic factors such as small tumor size, low SBR grade, the absence of axillary lymph node metastasis and vessel invasion; 6) the preliminary SAMBA analysis of ER-ICA in tissue sections, imprints and fine needle aspirates suggest that fine needle aspirates may not reflect accurately the tumor cell heterogeneity.
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PMID:[Immunohistochemical detection of estrogen receptors and image analysis (SAMBA 200) in breast carcinomas]. 317 38

The estrogen receptor (ER) content of 31 surgically removed breast tumors (26 duct carcinomas, one lobular carcinoma, one papillary carcinoma, one colloid carcinoma, one duct carcinoma in situ, and one atypical fibroadenoma) was determined by a commercially available immunocytochemical method (Abbott Laboratories, ER-ICA) on cytologic material obtained by fine needle aspiration biopsy (FNAB) of surgical specimens. Immunocytochemical staining of cells by a peroxidase-antiperoxidase technique was evaluated on the basis of the percentage of positive cells and the intensity of staining. An immuno-staining score for cytologic (IS-CYTO) and histologic (IS-HISTO) material was defined and a threshold of positivity determined to facilitate the semi-quantitation of results and the comparison of cases. The results of immunostaining of cytologic material were compared with the evaluation of ER in corresponding tissue samples as determined by the radioligand binding assay using the dextran-coated charcoal procedure (ER-DCC) and by ER-ICA using cryostat sections of frozen tissue. The sensitivity, specificity, predictive value of a positive test, and test efficiency of ER-ICA in cytologic material as compared to ER-DCC was 96%, 83%, 96% and 93%, respectively. The IS-CYTO was significantly correlated with the IS-HISTO in corresponding histologic material (r = 0.72, P less than 0.001). In conclusion, the combination of ER-ICA with FNAB represents a useful new technique for the evaluation of ER which may be applied to small primary tumors, tumor recurrences, and metastases.
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PMID:Evaluation of estrogen receptors by immunocytochemistry on fine-needle aspiration biopsy specimens from breast tumors. 330 9

Epidemiological and experimental investigations have led to the hypothesis that the growth of malignant melanoma is induced by hormones. The demonstration of free-hormone binding sites in melanoma tissue may help to determine the validity of this hypothesis, as receptors are necessary for the transformation of hormonal action. The DCC assay with subsequent saturation analysis was used for the demonstration of specific cytoplasmatic binding sites of steroid hormones. The presence of free-cytosolic estrogen-, progesterone- and glucocorticosteroid receptors was investigated in 50 melanoma samples from 46 patients. In 20 of the 50 specimens, free estrogen and progesterone receptors were found. Free-glucocorticosteroid receptors we found in 10 cases. The use of four fold-labeled estradiol (2,4,6,7-[3]-17 beta-estradiol) in the DCC assay produced a false-positive demonstration of free-estrogen receptors. Tyrosinase hydroxylates estradiol at the C2 level of the steroid. Using fourfold labeled estradiol, tritium is separated at the C2 position, thus forming radioactive water in the cytosol which mimics high, free-estrogen binding sites. The use of twofold-labeled estradiol or L-dopa in the experiments with fourfold labeled estradiol produced no false-positive determinations of estrogen receptors. The demonstration of receptors in malignant melanomas was unaffected by the sex of the patient. Also, the type of malignant melanoma, the invasion level, and the prognostic index did not show a correlation with the presence of the various hormone receptors. In metastases, free steroid hormone receptors were detected less often than in the primary tumor.
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PMID:[Steroid receptors in malignant melanomas]. 393 Apr 22

Colorectal carcinomas demonstrate extensive molecular genetic alterations throughout the genome. The genetic changes in cancer of the colon and rectum are among the best understood of any common human cancer. The genetic abnormalities include both dominant-acting oncogenes (Ki-ras, c-src) and tumor-suppressor genes which undergo inactivation or loss (APC, DCC, p53). The evolution of the cancer is a complicated and multistep process. At the various steps of this phenomenon we can recognize specific molecular genetic alterations. These particular genetic changes may be useful as improved markers to predict those patients who have an aggressive cancer of the colon, with occult metastases or increased metastatic capability and this selection of patients could lead to improved surgical and medical management.
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PMID:The genetic basis of colorectal cancer--clinical implications. 785 69

Human colon cancer development is associated with the accumulation of mutations and deletions in the suppressor genes DCC, APC and p53 and mutations in the dominant oncogene K-ras, with loss of wild type alleles. In earlier studies we had observed that about half of the resected human colon cancers placed into primary culture were growth stimulated by TGF beta 1. This group included the more advanced cancers which were either poorly differentiated primary-site cancers or metastases. In contract, the more differentiated colon cancers were inhibited or unaffected by TGF beta 1, indicating that a switch in response to TGF beta 1 occurs during colon cancer progression. Different sublines of the HT29 colon carcinoma cell line model the resected cancers, responding to TGF beta 1 by proliferation, inhibition or no growth modulation. The current study shows that while the poorly differentiated, TGF beta 1-stimulated sublines are most tumorigenic, all the sublines have the same spectrum of mutations: truncating mutations in both APC (adenomatous polyposis coli) alleles, no activated ras genes, mutated and thus overexpressed p53, and very low expression of DCC compared to normal colon cells. Genes other than the four already implicated in colon carcinoma evolution are responsible for the mitogenic response to TGF beta 1 found in the more advanced cancers.
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PMID:The capacity for growth stimulation by TGF beta 1 seen only in advanced colon cancers cannot be ascribed to mutations in APC, DCC, p53 or ras. 797 Jul 29

Genetic and environmental aspects play an important role in the development of colorectal cancer. However, the common molecular alteration in both hereditary and sporadic colon cancer is localized in the APC gene. the APC gene maps in the long arm of chromosome 5 and was discovered in patients with familial adenomatous polyposis (FAP). The search for the APC gene led to the identification of restriction fragment length polymorphisms (RFLPs) in FAP patients. Using these RFLPs in relatives of FAP patients it is possible to make the presymptomatic and prenatal diagnosis. The FAP syndrome is an interesting model of carcinogenesis in vivo. Thus the different stages involved in the FAP syndrome which include hyperproliferative epithelium, adenoma, adenocarcinoma and metastases, have allowed the analysis of molecular alterations in oncogenes and tumor suppressor genes. The APC gene alteration if not inherited, occurs as the earliest molecular alteration in the development of colorectal cancer whereas structural alterations of the genes myc, ras, p53, MCC and DCC are considered to be late events. All these investigations have lead to 1) a better understanding of the ethiology of cancer and 2) early diagnosis of colorectal cancer in both the hereditary and sporadic forms of the disease.
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PMID:[Molecular genetics of colorectal cancer and carcinogenesis]. 813 31


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