Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 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

Post-recurrence survival was examined in 62 breast cancer patients who had undergone curative radical mastectomies between 1974 and 1976 and suffered recurrences within 127 months of surgery. The prognostic value of 11 clinical, histological and genetic factors, including histologic grade of malignancy and amplification of oncogenes was analyzed using univariate and multivariate analyses. Not only the site of first recurrence, clinical stage and size of primary tumor at initial surgery, and disease-free period, but also histologic grade and amplification of the c-erbB-2 proto-oncogene were significant prognostic indicators of recurrent breast cancer. Multivariate analysis using Cox's regression model, histologic grade and amplification of c-erbB-2 in the primary tumor, as well as clinical stage at surgery and site of first recurrence, were shown to be major independent prognostic factors of recurrent breast cancer. Because post-recurrence prognosis was strongly influenced by the clinical, histological and genetic status of the primary breast cancer, appropriate evaluation of the primary tumor for the grade of aggressiveness of the cancer cells, as well as the extent of cancer spread, seem to be important.
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PMID:Prognostic factors for recurrent breast cancer: univariate and multivariate analyses including histologic grade and amplification of the c-erbB-2 proto-oncogene. 135 74

In order to verify whether the HER-2/neu gene is involved in the initial phases of neoplastic disease or in its progression, we evaluated the amplification and overexpression of this gene in the primary tumor and in synchronous metastatic axillary lymph nodes of 26 women with operable breast cancer. HER-2/neu was amplified in 35% and overexpressed in 33% of the primary sites; similar percentages were found in lymph nodes. The clear correlation between the two disease sites regarding gene, mRNA and protein levels, supports the hypothesis that this gene is involved in the initial and invasive phases of neoplasia. Its actual role with respect to other biological tumor characteristics during the metastatic process should be investigated further.
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PMID:HER-2/neu gene in primary and local metastatic axillary lymph nodes in human breast tumors. 163 21

Drawing upon the comprehensive population-based Northern Alberta Breast Cancer Registry containing 704 patients with histologically negative axillary lymph nodes who have been followed for 5-16 years, we have undertaken a retrospective case-control study to evaluate the utility of genomic amplification of specific protooncogenes [c-erbB-2 (nee HER-2/neu), c-erbA, c-myc, int-2, and hst-1] as predictive indicators of clinical outcome in node-negative disease. To this end, 115 women with node-negative breast cancer who had recurred at any time up to 16 years posttreatment (cases) were matched pairwise for appropriate clinicopathological variables (size of primary tumor, menopausal state, estrogen receptor status, anniversary year of treatment, and patient age) with a second group of 115 women (controls) selected from a cohort of 502 node-negative patients who had not relapsed during long-term follow-up. Tumor DNA extracted from archival formalin-fixed, paraffin-embedded tissue blocks were analyzed for protooncogene copy number by slot-blot hybridization. Taking a gene copy number of 3 as the cutoff, 27 of the 230 tumor samples examined contained from 3- to 22-fold elevation in c-erbB-2 genomic equivalents. Twenty-one of the 27 tumors amplified for c-erbB-2 were derived from cases and 6 from controls, signifying that 18% of the node-negative patients who had relapsed harbored excessive copies of the protooncogene in their malignant tissue compared to only 5% for the patients who had remained in remission. Accordingly, the occurrence of amplification of c-erbB-2 proved to be a statistically significant predictor of poor prognosis, especially disease-free interval (P = 0.006). Moreover, this genetic alteration appeared to be independent of and to have greater predictive power than most commonly used prognostic factors. Our findings also indicated that as a clinical test, measurement of c-erbB-2 amplification suffers from low sensitivity; however, when greater than 6 gene copies are present, the test has a positive predictive value for recurrence of 70%. Concurrent analysis of tumor DNA blots with probes for the other four protooncogenes examined revealed that their amplification, which others have reported to arise often, especially in node-positive disease, was seldom found even in our high-risk case group (2-3%). In short, our data strongly suggest that amplification of c-erbB-2 may contribute to the pathogenesis of some forms of node-negative breast cancer and thus may serve as a useful genetic marker to identify a subset of high-risk patients.
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PMID:Correlation between c-erbB-2 amplification and risk of recurrent disease in node-negative breast cancer. 167 Jul 62

Data regarding the prognostic value of HER-2/neu protein expression in breast cancer are conflicting, perhaps because of short follow-up and technical difficulties in the determination (the admixture of benign elements with the biochemical method and the subjectivity of the immunohistochemical assessment). Therefore, using digital image processing, we compared the correlation between and the prognostic value of (a) quantitative immunohistochemical HER-2/neu protein expression and (b) clinical, morphometric, and flow-cytometric DNA ploidy features; histologic grade; and biochemically assessed estrogen receptor content. Paraffin-embedded invasive breast Pancers of 82 patients with long-term follow-up were used. None of the patients had received adjuvant systemic therapy. HER-2/neu protein expression was significantly correlated with DNA index, lymph node status, and tumor size and, in the diploid tumors, was weakly correlated with the percentage of S-phase cells. Strong HER-2/neu protein expression was associated with a worse prognosis (although not significantly, p = 0.07). No differences were detected between cancers with or without axillary lymph node metastases. In survival analysis, the Multivariate Prognostic Index and the morphometric features were much stronger prognosticators than HER-2/neu protein overexpression, which, however, had additional prognostic value to that of many of the features analyzed, especially when more than 35% HER-2/neu protein levels (relative to the high expression SKBR3 cell line) were present. Combined diploidy and HER-2/neu protein content greater than 35% occurred in a small group of patients (n = 3), all of whom died. Likewise, in tetraploid cancers a combination of S-phase cells greater than or equal to 7% and HER-2/neu protein content greater than 35% was an ominous sign. In multivariate analysis, strong HER-2/neu protein overexpression was prognostically over-shadowed by the morphometric features. Nevertheless, it is important to further analyze the intriguing possibility of identifying a subgroup of breast cancer patients with a very poor outcome merely using cytometric analysis of paraffin-embedded material of the primary tumor.
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PMID:Comparative long-term prognostic value of quantitative HER-2/neu protein expression, DNA ploidy, and morphometric and clinical features in paraffin-embedded invasive breast cancer. 167 89

Esophageal and gastric cancers are highly virulent tumors with an especially poor prognosis. They are rather common tumors in the United States with an anticipated annual incidence of approximately 32,000 new patients in 1991. Adenocarcinomas of the proximal stomach and lower esophagus are rapidly increasing in incidence; the reasons for this remain unclear. Endoscopic ultrasonography has offered a new dimension to staging especially of the primary tumor but also shows promise for more accurate identification of nodal metastasis. While stage remains the single most important prognostic variable, biological studies investigating tumor markers are a high priority; aneuploidy and HER-2/neu amplification or overexpression may predict poor outcome in gastric cancer. Esophageal and gastric cancers have a high local and distant failure rate when treated with conventional therapy. New developments in chemotherapy in the neoadjuvant and postoperative setting are under intense investigation in an attempt to improve prognosis for these diseases.
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PMID:Therapy of upper gastrointestinal tract cancers. 174 44

The nuclear DNA ploidy pattern and c-erbB-2 oncoprotein expression in primary and metastatic lesions were investigated using paraffin-embedded materials from 44 cases of colorectal carcinoma with hepatic metastases and 45 cases without hepatic metastases. The frequency of aneuploidy and positive staining of c-erbB-2 in primary tumor with hepatic metastases were significantly higher compared with those without hepatic metastases (p less than 0.05). There were significant correlations between diameter of metastases and DNA ploidy pattern of the metastases and between metachronous metastases, degree of metastases, vessel involvement and DNA ploidy pattern of the primary tumor. Positive staining of c-erbB-2 was detected more frequently with the advancement of depth of tumor invasion. There was no significant correlation between DNA ploidy pattern and c-erbB-2 expression. In the survival of patients whose primary tumor and hepatic metastases were resected, it was shown that DNA ploidy pattern of metastases was the most important independent prognostic factor. Expression of c-erbB-2 in primary tumor predicted the hepatic metastases.
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PMID:[DNA content and c-erbB-2 oncoprotein expression in hepatic metastases from colorectal carcinoma--in relation to clinicopathologic findings and prognosis]. 196 Nov 85

Amplification of the HER-2/neu oncogene was determined in 362 tumors from patients with primary breast cancer (185 node-positive patients and 177 node-negative patients). The overall amplification rate was 33% (30% for node-negative patients; 31% for patients with 1-3 positive nodes; 40% for patients with greater than 3 positive nodes). Gene copy number was not associated with axillary lymph node status, steroid receptor status, or patient age but was weakly correlated with the size of the primary tumor. Amplification of the HER-2/neu gene did not correlate with either disease-free or overall survival in univariate or multivariate analyses. The results were unambiguously negative for patients with node-negative disease. Although the univariate results for node-positive patients were marginally significant (P = 0.07), the significance was not retained in multivariate analyses. Thus, while HER-2/neu amplification may be biologically important in primary breast cancer, it will only be of marginal utility as a prognostic factor for predicting clinical outcome.
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PMID:Follow-up study of HER-2/neu amplification in primary breast cancer. 198 36

Murine studies have documented the relationship between surgical curability of a breast cancer and fertility cycle stage at the time of primary surgical resection. In a retrospective study of 41 premenopausal women with primary breast cancer followed for 6 to 14 years, disease recurrence was more frequent and more rapid in women whose initial tumor resection was performed during the perimenstrual period (days 0-6 and 21-36) than during the periovulatory period (days 7-20) of the menstrual cycle. Patients in both groups had disease of equal severity as measured by size of primary tumor, extent of lymph node involvement, estrogen and progesterone receptor assay determination, flow cytometry, and HER-2/neu gene amplification. To date, with 100% follow-up, 7 of the 19 perimenstrual patients (37%) have relapsed and 6 (32%) have died of metastatic disease. Only 3 of the 22 periovulatory patients (14%) have relapsed and only 1 (5%) has died of metastatic disease. These results, predicted by a murine experimental model, suggest that the endocrine milieu at the time of primary tumor resection impacts upon breast cancer prognosis.
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PMID:The effect of surgical timing within the fertility cycle on breast cancer outcome. 200 89

In order to examine the role of the erbB-2 oncogene in human breast cancer, gene amplification and expression were examined in multiple stages of tumor progression. Gene amplification ranging from 2-fold to 32-fold was found in 30 (29%) of 130 cases analyzed. Expression of the receptor-like gene product was determined by a combination of Western immunoblotting and immunohistochemistry. In each case of gene amplification, there was high level overexpression (+ + +) of the protein product. In an additional 29 of 111 cases in which expression was studied (26%), there was moderate level overexpression (+ +) of erbB-2 in the absence of gene amplification. Amplification and overexpression of the erbB-2 gene were found in early clinical stages of breast cancer as well as in more advanced cases. In 23 patients, gene number and level of gene expression were equivalent in the primary tumor site compared with single or multiple metastatic sites in regional lymph nodes. Using a combination of immunohistochemistry and in situ cytohybridization, high (+ + +) and moderate (+ +) level overexpression were homogeneously present in all malignant epithelial cells within histological sections of both primary and metastatic tumor. The intraductal component of carcinoma was identified in sections from 16 invasive primary tumors. erbB-2 gene expression in the intraductal lesions was equivalent to or exceeded expression in the infiltrating components of these tumors. Because erbB-2 alterations are (a) present in all clinical stages, (b) maintained during metastatic spread, (c) homogeneously present throughout tumor sections, and (d) present in the in situ as well as infiltrating component, we conclude that these alterations are selected for early and may be important in the initiation of certain mammary cancer.
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PMID:Increased erbB-2 gene copies and expression in multiple stages of breast cancer. 220 36


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