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)

In an attempt to evaluate the relationship between c-erbB-2 expression and/or gene amplification, DNA ploidy and morphology, wall penetration, lymphatic permeation, and vascular invasion, we studied a series of 87 primary gastric carcinomas and their respective metastases (n = 335) using immunohistochemistry and performed DNA analysis of 30 primary tumors and 10 metastases from eight cases. Flow cytometry of fresh or frozen material was performed in 79 primary tumors. Five out of 87 primary tumors (5.7%) and 17 out of 335 lymph node metastases (5.1%) showed unequivocal membrane immunostaining for c-erbB-2. Seven out of 30 primary tumors (23.3%) showed gene amplification while amplification was identified in four out of 10 metastases (40.0%) from three patients. Eight tumors (9.2%) showed c-erbB-2 protein immunoreactivity, gene amplification, or both. One of these cases showed c-erbB-2 protein immunoreactivity only in the metastatic deposits, while gene amplification could be identified in the primary tumor. Three primary tumors showed gene amplification, but immunoreactive cells could not be identified. In no case was protein overexpression identified in the absence of gene amplification. Five cases with c-erbB-2 expression/amplification were well/moderately differentiated, and all the eight cases with c-erbB-2 expression/amplification disclosed aggressive features. Lymphatic permeation/lymph node metastases were found in all the cases and seven cases showed vascular invasion as well. In one case, there was also a liver metastasis. Two cases were early gastric carcinomas (T1sm) showing lymphatic permeation/nodal metastases and venous invasion. Six cases were aneuploid.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:c-erbB-2 expression in primary gastric carcinomas and their metastases. 135 80

Human endometrial adenocarcinoma cells (Ishikawa line) constitutively express c-erbB2 coded oncoprotein p185erbB2 (p185) which is believed to be an orphan receptor for an unknown growth factor. Since we have shown that expression of p185 in primary lesions of endometrial cancer correlates well with high frequency of lymph node++ metastases and that the metastatic cells in the nodes strongly expressed p185, the role of the oncoprotein in processes of metastases was studied. Culturing the cells in the presence of 15% FCS and with monoclonal antibody to the extracellular domain of p185 (CB-1) inhibited cell growth and attenuated p185 expression on Western blotting, whereas no change occurred with the control antibody. Cells cultured without FCS achieved only approximately 1/3 growth compared to cells with FCS, and further suppression of growth was observed after adding CB-1. When cells were cultured on human term amnion, basement membrane invasion with p185 expression was observed. In nude mice, intraperitoneal seeding resulted in implant formation which was also associated with positive p185 as well as cyclin immunohistochemistry. In the two experiments, treatment of cells with CB-1 inhibited invasion or implant formation. The present study suggests that a signal through p185 receptor molecules acts as a trigger for early proliferation, and interaction with the host may enhance up-regulation of p185.
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PMID:[Role of p185c-erbB2 in endometrial cancer growth in vitro]. 135 38

In breast cancer the tumor stage, axillary lymph node metastases and hormone receptors are well established prognostic factors. Nevertheless, additional prognostic factors are still desirable. Recently, attention has focussed on molecular markers, in particular mutated genes involved in the pathogenesis of breast carcinoma. The first such marker to be tested for its clinical relevance has been the c-erbB-2 oncogene. However, the results of the many studies published on this subject are controversial. Further progress can be expected from two different strategies. The molecular pathogenesis of breast cancer must be elucidated in more detail, since it is likely that breast cancer is the result of a progressive accumulation of many different somatic mutations in diverse genes such as oncogenes and tumor-suppressor genes. Rather than relying on retrospective analyses, the clinical relevance of new markers must be tested in prospective clinical trials.
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PMID:[Current molecular prognostic factors in breast carcinoma]. 135 43

In a retrospective study the expression of the c-erbB-2 oncogene was determined immunohistochemically in 276 breast cancer samples from 253 patients with the antibody 21N. The follow-up period was between 7 and 12 years. This study showed a trend for an inverse relationship between c-erbB-2 positive tumours and estrogen receptors (ER). A correlation was assessed between c-erbB-2 positive tumours and histological grade, liver metastases as first site of metastases, disease free survival time (DFS) in the second and third year after diagnosis and overall survival time (OST) in the third and fourth year after diagnosis. A trend was seen between c-erbB-2 positive tumours and tumour size. No correlation was found between c-erbB-2 positive tumours and age at diagnosis. The method of operation and lymph node involvement. From this study we conclude that there is a significant difference in prognosis the first years after diagnosis, but this difference seems to vanish in a longer follow-up period of 12 years. This provides us with an explanation for the discrepancies in literature concerning c-erbB-2 expression and prognosis in breast cancer. Some investigators did not show differences in prognosis between positive and negative cases after a long follow-up period whereas investigations with a short term follow-up period up to 2-3 years have indeed established a more aggressive behaviour of c-erbB-2 overexpressionary tumours.
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PMID:c-erbB-2 positive breast tumours behave more aggressively in the first years after diagnosis. 135 63

Oncogene expression has been found to be a potential marker for aggressive biologic behavior in certain tumors. We studied 21 follicular adenomas and 20 follicular carcinomas by immunocytochemistry utilizing specific monoclonal antibodies against HER-2/neu and c-myc oncogenes. Survival data were obtained from our institution's tumor registry. No expression of the HER-2/neu oncogene was found in the specimens studied. Cytoplasmic staining for c-myc was observed in 3 of 21 adenomas (14%) and 9 of 20 (45%) carcinomas (p < 0.05). The incidence of local, regional, and distant metastases was not significantly different in c-myc (+) and c-myc (-) patients. The c-myc oncogene is expressed more often in malignant than in benign follicular neoplasms of the thyroid, but its expression does not appear to be a good prognostic indicator.
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PMID:Oncogene expression in follicular neoplasms of the thyroid. 136 Nov 6

The rat neu gene is known to be activated by a point mutation in its predicted transmembrane domain. Overexpression of the human homologue of neu, the c-erbB-2 gene, in human lung cancer has been reported, and a similar activating point mutation has been suggested. Therefore, we tested for possible aberrations of the c-erbB-2 gene in the region of the transmembrane domain in surgical specimens of human primary lung cancer from 190 patients, and also examined 24 metastases and 26 specimens of noncancerous portions of the lung of the same patients. Single-strand conformation polymorphism analysis of polymerase chain reaction products revealed no point mutations in the target domain in any of these specimens.
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PMID:Absence of activating mutations in the transmembrane domain of the c-erbB-2 protooncogene in human lung cancer. 148 46

Tumorigenesis is a multistep process involving mutations of dominantly acting proto-oncogenes and mutations and loss-of-function mutations of tumor suppressor genes. Some of these mutations may be inherited, but most of them are acquired. Models for the sequential steps of the genetic changes involved in tumor development have been proposed for certain cancers, such as colon cancer. In the case of ovarian cancer, relatively little is known about the genetic events associated with the initiation or subsequent progression and metastases of the tumor. Cytogenetic analysis has revealed a high incidence of both structural and numerical chromosome changes, and the extent of these changes seems to increase with tumor progression. Oncogene activations of the proto-oncogenes K-ras, c-myc and c-erbB-2 have been found more frequently in aggressive ovarian tumors and may be associated with poor survival. Tumor-specific allele loss involving putative tumor suppressor genes has been observed for loci at chromosomes 11p, 17p, and 17q,--loci commonly deleted in other cancers too. A relatively high incidence of allelic loss on chromosome 6q appears to be specific to ovarian carcinoma. Familial breast/ovarian cancer has been suggested to map to chromosome 8q. Recently we have found a germ-line mutation in the tumor suppressor gene p53 in a family with breast- and ovarian cancers, indicating that this is the predisposing gene in this family. Genetic changes important for the etiology of ovarian cancers seem to involve both somatic mutations of oncogenes and somatic or germ-line inactivation of tumor suppressor genes.
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PMID:Oncogenesis in ovarian cancer. 150 89

The c-erbB-2 protooncogene encodes a possible growth factor receptor. This gene has been studied as to whether it can be regarded as a prognostic indicator in human breast carcinoma. As amplification and overexpression of the gene have been reported in several adenocarcinomas, 24 specimens of human gastric cancers were examined by immunohistochemical staining (24 cases), by Southern blotting (23/24) and by Northern blotting (16/24). Amplification of the gene was detected in two moderately differentiated tubular adenocarcinomas (8.7%), and overexpression of c-erbB-2 mRNA was detected in three moderately differentiated tubular adenocarcinomas (18.8%). By immunohistochemical staining of paraffin-embedded tissues using a polyclonal antibody to c-erbB-2 gene products, the cell membrane was stained positively in three cases of gastric cancers which overexpressed c-erbB-2 mRNA. Peritoneal metastases were found in six gastric cancers, including two moderately differentiated tubular adenocarcinomas in which amplification of c-erbB-2 occurred. These results suggest that amplification and overexpression of c-erbB-2 may be correlated with metastases in differentiated adenocarcinoma of the stomach.
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PMID:Amplification and overexpression of the c-erbB-2 protooncogene in human gastric cancer. 157 21

Prior studies have shown that overexpression of HER-2/neu occurs in one third of breast and ovarian cancers and that overexpression is associated with poor prognosis. We used a monoclonal antibody to assess immunohistochemically the level of HER-2/neu expression in normal and malignant endometrium. In 24 normal endometrial samples light to moderate (1+ to 2+) staining for HER-2/neu was seen in the glands, and there was no variation in intensity of staining during the menstrual cycle. Among 95 endometrial adenocarcinomas, nine (9%) were found to have heavier staining for HER-2/neu than was seen in normal endometrium (3+). High expression of HER-2/neu was found in 27% of patients with metastatic disease compared with 4% of patients with disease confined to the uterus (p less than 0.005). High HER-2/neu expression also was associated with absence of estrogen receptor (p less than 0.005) and with increased mortality from cancer. Further studies are needed to determine the significance of HER-2/neu overexpression in endometrial cancer.
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PMID:Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease. 167 Sep 8

Using a polyclonal antibody that is monospecific for the erbB-2 oncogene product, an immunohistochemical study of the expression of erbB-2 protein was performed in formalin-fixed paraffin-embedded tissue sections from 260 primary gastric cancers. erbB-2 protein expression in which the reaction was localized to the cell membranes was observed in 31 (11.9%) cancers. All nontumor cells and normal gastric epithelium were negative for membrane staining. There was not a significant association between erbB-2 staining and histological type or venous invasion. erbB-2 protein expression was associated with serosal invasion, lymph node metastasis, and lymphatic invasion. In addition, erbB-2 protein expression correlated with a high number of lymph node metastases. Furthermore, the risk of recurrence in lymph node was over 3 times higher in patients with erbB-2 protein-positive tumors than in those with erbB-2 protein-negative ones. When erbB-2 protein expression and the clinical parameters were entered simultaneously into the Cox regression model, erbB-2 protein expression emerged as an independent prognostic indicator. Patients with erbB-2 protein-positive tumors had 5-fold greater relative risk of death, as compared with those with erbB-2 protein-negative tumors. These results indicate that erbB-2 protein expression is an important independent prognostic indicator in gastric cancer. The high malignant potential of erbB-2 protein-positive tumors may be associated with the very high potential for lymph node metastasis.
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PMID:Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer. 167 Sep 98


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