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)

The expression of amphiregulin (AR), heregulin (HRG), and cripto-1 (CR-1) mRNA transcripts was assessed in 60 human primary breast carcinoma. AR and HRG transcripts were expressed respectively in 58% and 25% of the carcinomas as measured by Northern blot analysis. CR-1 mRNA was found in 77% of the carcinomas using Reverse Transcriptase-PCR analysis. Coexpression of two or three of these peptides was observed in several specimens. There was no significant association between AR, HRG, and CR-1 expression and nodal status, EGF receptor, or c-erbB-2 protooncogene expression in these tumors. However, a significant association between AR expression and estrogen receptor positivity was observed.
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PMID:Expression of messenger RNA for amphiregulin, heregulin, and cripto-1, three new members of the epidermal growth factor family, in human breast carcinomas. 757

We have determined the average gene copy numbers (AGCN) of the erbB-1 gene, encoding the epidermal growth factor receptor (EGF-R), the erbB-2 and the erbB-3 genes in breast, ovarian, oral, and lung cancer tissue by using double-differential PCR (ddPCR). The ddPCR method comprises the co-amplification of the single-copy gene HBB, the erbB-1, erbB-2 and erbB-3 oncogenes and the second single-copy reference gene SOD2 under equal reaction conditions. In a retrospective study the AGCN of the erbB genes and the time up to the appearance of metastases were subjected to life-table analysis in 128 women with primary breast cancer. Patients whose breast cancer tissue showed an AGCN for erbB-1 of less than 0.4 and greater then 1.6, as expected from the literature, for erbB-2 of greater than 2.0 and for erbB-3 of less than 1.75 had decreased disease-free survival (DFS). The quotient of erbB-1 and erbB-2 AGCN was the most significant in multivariate Cox analysis followed by nodal status and progesterone receptor status. In extensive studies a similar association between erbB AGCN and metastasis was seen in ovarian cancer and oral cancer, though erbB oncogene aberrations in those entities were not as frequent as in breast cancer. The AGCN of erbB oncogenes may not be of prognostic value in untreated lung cancer patients.
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PMID:Prognostic relevance of aberrations in the erbB oncogenes from breast, ovarian, oral and lung cancers: double-differential polymerase chain reaction (ddPCR) for clinical diagnosis. 760 71

We studied c-erb-B2 gene amplification of DNA of primary breast tumours without distant metastasis from 236 women admitted to our institute during 1992. For 125 of them, we had a serum sample at diagnosis, before any treatment. C-erb-B2 gene amplification (> or = 2 copies) was observed in 26% (62/236) of the cases. There was a correlation with higher histological grades (p < 0.03) and with absence of hormone receptors: ER-(p < 0.0001). PgR-(p < 0.0001), association ER- and PgR-(p < 0.0000). Large tumours T3 and T4 taken together tended to present more c-erb B2 gene amplifications (p < 0.08). There was no correlation with age, histological type or nodal status. At diagnosis, mean concentration of serum c-erb-B2 oncoprotein was 8.5 +/- 18 U/ml with a median of 4 U/ml (4-150). Choosing a cut-off value of 8 U/ml gave a sensitivity of 21% (26/125). Serum levels of c-erb-B2 oncoprotein were correlated with tumour spread: large tumours T3-T4 (p < 0.001), nodal involvement (N+) (p < 0.01), association T3-T4 and N+(p < 0.0005), high levels of CA 15:3 (normal value < 25 IU/ml) (p < 0.05). There was no other correlation, particularly with age, histological type, hormone receptors or c-erb-B2 gene amplification. c-erb-B2 oncoprotein serum levels could be helpful to detect recurrences. Assessment of c-erb-B2 oncoprotein serum concentration, before treatment, as an independent prognostic factor is necessary.
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PMID:C-erb-B2 gene amplification and serum level of c-erb-B2 oncoprotein at primary breast cancer diagnosis. 784 May 6

We have analyzed amplification of the c-erbB-2 and int-2 genes, and restriction fragment length polymorphisms (RFLPs) of the int-2 gene in 105 primary breast carcinomas. In 90 of 105 samples, overexpression of the c-erbB-2 protein and the DNA ploidy pattern were also analyzed. Amplification of the c-erbB-2 and int-2 gene was found in 27% and in 17%, respectively. No statistical correlation between c-erbB-2 and int-2 genes amplification was observed. Overexpression of the c-erbB-2 protein was detected in 28% of samples. A correlation was observed between amplification of the c-erbB-2 gene and positive nodal status. Amplification of the int-2 gene showed no correlation with clinicopathological parameters, except that a significantly higher incidence of amplification was observed in breast carcinoma with more than 4 positive lymph nodes. Genotypes of the int-2 gene identified by RFLPs analysis revealed no correlation with clinicopathological parameters. DNA ploidy pattern, which showed neither correlation with c-erbB-2 nor int-2 genetic alterations, was associated with tumor size and TNM classification. Our result suggests that analysis of genetic alterations of the c-erbB-2 and int-2 genes and the DNA ploidy pattern may be a useful adjunct in the assessment of aggressiveness of breast carcinoma.
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PMID:[The significance of c-erbB-2 and int-2 gene alterations and DNA ploidy pattern for aggressiveness of breast cancer]. 790 48

c-erbB-2 DNA amplification and mRNA expression were analyzed by dot and Southern blots in 65 human primary breast tumors. Gene amplification was observed in 21 of 65 (32.3%) and elevated levels of c-erbB-2 transcript in 14 of 60 (23.3%) of the tumors analyzed. Only 55% of the tumors with c-erbB-2 gene amplification presented gene overexpression, showing an incomplete correlation between gene amplification and overexpression. No statistically significant correlation was observed between c-erbB-2 genetic alterations and other prognostic factors in breast cancer. However, patients with tumors presenting c-erbB-2 gene amplification and/or overexpression appeared to have a shorter disease-free interval than patients without c-erbB-2 genetic alterations. High levels of c-erbB-2 gene amplification were more powerful predictors of risk of recurrence than was overexpression of the gene. Cox univariate-bivariate analyses suggested that gene amplification was independent of nodal status to predict recurrence in breast cancer.
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PMID:Genetic alterations in c-erbB-2 protooncogene as prognostic markers in human primary breast tumors. 790 24

Immunohistochemical c-erbB-2 protein overexpression was detected in 34 of 124 (27.4%) paraffin-embedded breast cancer specimens. Although no difference was seen between the c-erbB-2 positive and negative groups in 5-year disease-free survival, 5-year overall survival was significantly less favorable in the c-erbB-2 positive group. Furthermore, patients graded as having positive c-erbB-2 staining and aneuploid DNA showed significantly poorer survival than those in other categories. The significant prognostic factors, determined by a multivariate analysis, were nodal status and c-erbB-2 overexpression. Our findings therefore suggest that c-erbB-2 expression is a prognostic factor in breast cancer and that it could be useful in the determination of postoperative adjuvant therapy.
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PMID:Immunohistochemical overexpression of C-erbB-2 in the prognosis of breast cancer. 790 3

To verity the role of metastasis-related nm23 genes in carcinogenesis and progression of ovarian carcinoma, we analyzed the mRNA levels of the nm23 genes of both isoforms, -H1 and -H2, together with those of the epidermal growth factor receptor, the c-erbB-2, and the c-erbB-3 genes in 45 ovarian carcinomas and 5 benign cystadenomas. Expressions of nm23 gene products/nucleoside diphosphate kinases, epidermal growth factor receptor, erbB-2 protein, and sex steroid receptor status in ovarian carcinomas were also examined by immunohistochemistry. The mRNA levels of nm23-H1 and nm23-H2 were higher in carcinoma tissues compared with benign tumors (H1, P < 0.01). The mRNA levels of c-erbB-2 and c-erbB-3 were also elevated in carcinoma tissues, and there was a positive correlation between mRNA levels of the nm23-H1 and the c-erbB-2 genes (r = 0.58; P < 0.05). Correlation of immunohistochemical staining between nucleoside diphosphate kinases and erbB-2 protein was also observed in ovarian carcinoma tissues. Sex steroid receptor positivity was related to a higher expression of nucleoside diphosphate kinases. Expression levels of the nm23 genes in ovarian carcinomas were not related to either histological subtype or local extension and peritoneal dissemination. Among stage III ovarian carcinomas, however, tumors possessing lymph node metastasis showed significantly lower nm23-H1 mRNA levels than those without nodal involvement (P < 0.05). Stage IV carcinomas also exhibited lower nm23-H1 and nm23-H2 expression levels compared with other stages (P < 0.05). These results suggest that expression of the nm23 genes, especially nm23-H1, is activated, accompanied by c-erbB-2 and c-erbB-3 overexpressions, in early stages of the carcinogenic process of ovarian carcinoma and reduction of nm23-H1 expression occurs in association with lymph nodal and/or distant metastasis.
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PMID:Expression of metastasis-related nm23-H1 and nm23-H2 genes in ovarian carcinomas: correlation with clinicopathology, EGFR, c-erbB-2, and c-erbB-3 genes, and sex steroid receptor expression. 790 45

There is increasing evidence that genes involved in normal cell growth and differentiation (oncogenes) or genes that encode for growth factors are important in determining the development and biologic aggressiveness of gastric carcinoma. This study was undertaken to define the prognostic value of the overexpression of p53 protein, c-erbB-2 protein, EGFr protein and PCNA in gastric carcinomas. Using monoclonal antibodies, immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue sections from 84 primary gastric carcinomas. Overall, 34% of gastric carcinomas had nuclear-staining for p53 protein, 34% of carcinomas membrane staining for the c-erbB-2 and 74% of carcinomas membrane and cytoplasmic staining for EGFr, showing distribution in a heterogeneous fashion. PCNA was expressed as Grade 2 and 3 in 75% of patients with gastric carcinomas. Both c-erbB-2 and p53 staining was significantly associated with high grade expression of PCNA. p53 staining tended to be associated with positive nodal status and metastasis, and c-erbB-2 staining with positive nodal status only. Multivariate analysis using the Cox model showed that overexpression of p53 protein, c-erbB-2 protein and PCNA was not an independent prognostic variable in gastric carcinoma. These results suggest that expressions of p53 and c-erbB-2 protein are heterogeneous and that p53 and c-erbB-2 overexpressions are significantly associated with high proliferative activity in gastric carcinoma.
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PMID:Immunohistochemical detection of p53 protein, c-erbB-2 protein, epidermal growth factor receptor protein and proliferating cell nuclear antigen in gastric carcinoma. 791 Oct 25

We have conducted two series of studies, a biochemical study and an immunocytochemical study, to investigate the role of epidermal growth factor receptor (EGFR) expression in primary breast cancer patients. In the biochemical study, a consecutive 115 patients were included and EGFR was measured by a competitive binding assay with multipoint Scatchard analysis. In the immunocytochemical study comprising 126 patients, EGFR status was determined by immunostaining with anti-EGFR antibody EGFR1. Several agreements were found from these two studies. EGFR status was inversely correlated with estrogen receptor (ER) status. No significant correlation was found between EGFR status and tumor size, nodal metastases, or the expression of c-erbB-2 protein. Ki-67 immunoreactivity, a cellular proliferation marker, was enhanced in EGFR positive tumors over EGFR negative tumors, suggesting a linkage of EGFR expression to cellular proliferative activity. Post-operative follow up showed that relapse-free survival for EGFR positive patients was significantly worse than that for EGFR negative patients, particularly in node-positive patients. Multivariate analysis demonstrated a significance of EGFR status as an independent prognostic indicator in primary breast cancer. The group expressing EGFR and c-erbB-2 protein indicated a particularly high risk for relapse.
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PMID:Role of epidermal growth factor receptor expression in primary breast cancer: results of a biochemical study and an immunocytochemical study. 791 67

The protein product of c-erbB-2 and ras oncogene has been examined for its prognostic potential in both node positive and node negative breast cancer. Using a western blot analysis, levels of these proteins were determined in 159 primary human breast tumor specimens. We examined relationships between gene expression and coexpression with other established markers of prognosis, as well as clinical outcome. Multivariate analysis showed that nodal involvement was the most powerful prognostic factor for predicting overall survival (< 0.000) and disease-free survival (p = 0.001), whereas c-erbB-2 expression was second only to nodal status for predicting overall survival in the whole series (p = 0.05). A separated stepwise analysis was conducted for node negative patients who did not receive any kind of adjuvant treatment and for node positive ones who underwent adjuvant chemo or hormonotherapy. c-erbB-2 expression independently predicted poor survival among node negative tumors (p = 0.001) and was associated with ras expression among node positive cases (p = 0.04). If adjuvant treatment is included in the model, coexpressing tumors are less responsive to Tamoxifen and CMF regimens than those with low levels of protein expression (p = 0.04). These results are potentially of clinical value in separating a subset of node positive breast cancer patients for more intense postsurgical treatment. Among node negative patients, the sole expression of c-erbB-2 enhanced levels, is more likely to retain a predictive value in relation to the response after conventional adjuvant treatment.
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PMID:Prognostic and predictive relevance of c-erbB-2 and ras expression in node positive and negative breast cancer. 791 96


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