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)

A system of histologic grade of malignancy in human breast carcinoma was devised by significantly modifying the way of evaluating number of mitoses and architectural atypia in the histologic grading of Bloom and Richardson. The modified grading system was applicable to all histologic subtypes of adenocarcinoma and showed a good association with prognosis of breast carcinoma patients in retrospective analysis of 176 consecutive surgical cases (P less than 0.0001). Of the three components of histologic grade, architectural atypia and number of mitotic figures independently had a significant effect on the prognosis. The copy number of c-erbB-2, a prognostic factor independent of tumor size and nodal status, was strongly correlated with the histologic grade, number of mitotic figures, and degree of nuclear atypia (P less than 0.001, each). Cox's regression model analysis showed that nodal status and histologic grade were two determinants of prognosis, and the independent effect of c-erbB-2 amplification was absorbed within that of the histologic grade. Although the importance of c-erbB-2 gene copy number seemed to be inferior to that of the histologic grade, both were shown to be strongly associated with the aggressiveness of the tumor itself rather than the extent of tumor spread.
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PMID:Correlation between histologic grade of malignancy and copy number of c-erbB-2 gene in breast carcinoma. A retrospective analysis of 176 cases. 215 4

C-erbB-2 and epidermal growth factor receptor (EGFR) genes were independently shown to be associated with breast cancer progression. In this report, we have analyzed the structure and expression of these 2 genes in the same tumor specimens of a large series of breast cancers. Two clinical types of tumor were studied: inflammatory (IBC) and non-inflammatory breast cancers (NBC) obtained from 221 untreated patients at different clinical stages. Amplification and over-expression of the c-erbB-2 proto-oncogene were observed in 27% and 47% of tumors, respectively, and were strongly associated with breast cancers of the most unfavorable prognosis, namely IBC and NBC with multiple positive axillary nodes. EGFR gene was neither amplified nor rearranged. A restriction fragment length polymorphism (RFLP) for HindIII endonuclease was observed. EGFR transcripts were detected in 46% of tumors and observed more frequently in IBC than in NBC (p less than 0.02). In NBC the presence of EGFR transcripts increased linearly with lymph-node involvement and was associated with estrogen-receptor-negative tumors (p = 0.01). Analysis of both genes from the same tumor samples indicated that genes are associated with cancer aggressiveness. Furthermore, in NBC these 2 genes were independently activated, in contrast to IBC in which activated genes were negatively correlated, suggesting that c-erbB-2 and EGFR genes play different roles in NBC and IBC.
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PMID:Structure and expression of c-erbB-2 and EGF receptor genes in inflammatory and non-inflammatory breast cancer: prognostic significance. 256 19

Amplification of the c-erbB-2 proto-oncogene was detected in 10% of 122 primary human breast tumors examined. Examination of patients' histories with a post-surgical median follow-up time of 53 months suggested no statistically significant association between the increased copy number of c-erbB-2 proto-oncogene in breast tumors and several oncological disease parameters, such as histopathological grading, ovarian hormonal status, age, number of positive lymph nodes, time to relapse, and survival period. Results of the analysis of matched sets of primary tumors and lymph node metastases were also consistent with the lack of a strong association between increased copy number of c-erbB-2 proto-oncogene and aggressiveness of tumors.
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PMID:Lack of evidence for the prognostic significance of c-erbB-2 amplification in human breast carcinoma. 322 22

There are few reliable prognostic markers of biological aggressiveness for head and neck carcinomas in general. For salivary gland carcinomas, anatomic location, tumor size, histological grade, and extent of disease involvement are considered to be clinically important risk factors for recurrent disease. Molecular genetic alterations in salivary gland carcinomas have not been characterized, and tumor cell proteins have not been shown to be prognostically significant. Here a cohort of mucoepidermoid carcinomas of the major (parotid and submandibular) salivary glands are analyzed for a molecular genetic alteration, HER-2/neu gene amplification, and gene amplification and expression results are compared with long-term clinical follow-up information. Archival tissues resected from 58 patients with mucoepidermoid carcinoma of salivary glands were evaluated for HER-2/neu gene amplification by fluorescence in situ hybridization and for gene expression by immunohistochemistry in a blinded fashion. Clinical follow-up information was compared with the results of these analyses to determine whether there were significant associations. Overexpression, identified as membrane immunostaining by immunohistochemistry, was observed in 22 of 58 (38%) mucoepidermoid carcinomas. Gene amplification, characterized by fluorescence in situ hybridization, was observed in 12 (21%) cases. Eleven of the 12 cases with gene amplification were also immunostained for HER-2/neu. Both gene amplification (P = 0.0001, P < 0.0001) and immunostaining (P < 0.0001, P < 0.0001) were correlated with shorter disease-free interval and poorer overall patient survival, respectively. Multivariate analysis showed that HER-2/neu immunostaining and amplification were markers of poor prognosis independent of histopathological grade, tumor size, and involvement of regional lymph nodes. HER-2/neu is amplified and/or overexpressed in approximately one-third of mucoepidermoid carcinomas of salivary glands. Amplification and/or overexpression appears to be an independent marker of poor prognosis in mucoepidermoid carcinomas of the salivary glands as it is in carcinomas of the breast, ovary, and endometrium.
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PMID:Amplification and overexpression of HER-2/neu in carcinomas of the salivary gland: correlation with poor prognosis. 752 62

The mutation of the p53 gene is a common phenomenon in numerous human tumors, leading to the accumulation of nonfunctioning p53 protein in the cell nucleus, which can be detected by immunohistochemistry. In breast cancer, it has been suggested that the overexpression of p53 protein in the nucleus is an indicator of poor prognosis, which must be borne in mind in selecting coadjuvant treatment for each patient. This study is an immunohistochemical analysis of p53 expression in 153 cases of mammary carcinoma, correlating it with histological grade, axillary node status, hormone receptors, cell-proliferation fraction and expression of the c-erbB-2 oncoprotein. Of all the breast-cancer tissue analyzed, 43.79% was positive for p53. The overexpression of this protein bears a direct statistically significant relationship to histological grade, cell-proliferation fraction and c-erbB-2, and an inverse relationship to estrogen and progesterone receptors. No statistically significant relationship was found with axillary node status. The expression of p53 in poorly differentiated tumors-commonly receptor negative and with a high proliferation fraction-may indicate greater tumor aggressiveness and a high risk of relapse.
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PMID:p53 in breast cancer. Its relation to histological grade, lymph-node status, hormone receptors, cell-proliferation fraction (ki-67) and c-erbB-2. Immunohistochemical study of 153 cases. 757 1

The expression of Cath-D c-erbB-2 and EGFR in breast cancer and its correlation of lymphatic metastases were studied in 277 cases by immunohistochemical technique. Positive staining of Cath-D was detected in 107 cases (38.62%), of which, 89 cases (83.17%) had documented metastasis in the lymph nodes. One hundred and seventy cases (61.38%) stained negative for Cath-D, of which 64 cases (37.64%) had detectable lymphatic metastases. There was a significant difference in the rate of the lymphatic metastases between the Cath-D positive and Cath-D negative groups (P < 0.0001). Fifty-six out of 107 Cath-D positive cases (52.34%) were c-erbB-2 positive as well. However, only 27 out of 170 Cath-D negative cases (15.88%) were c-erbB-2 positive. The positive rate of c-erbB-2 in Cath-D positive group was significantly different from that of Cath-D negative group (P < 0.0001). Among those 107 Cath-D positive cases, 49 cases (45.79%) were EGFR positive. Only 24 cases (14.12%) were EGFR positive among the 170 Cath-D negative cases. The positive rate of EGFR between these two groups was also significantly different (P < 0.0001). The results suggest that Cath-D status can be used as an indicator of the aggressiveness of the breast cancer. Breast cancer cases with a positive Cath-D staining are more likely to have lymphatic metastases and a poor prognosis. Therefore, alternative therapeutic strategies and close follow-ups are needed for these patients.
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PMID:[The expression of Cath-D, c-erbB-2 and EGFR in breast cancer and its correlation to lymphatic metastasis]. 765 92

The HER-2/neu proto-oncogene encodes a transmembrane receptor protein whose expression is enhanced in a number of breast and ovarian tumors and correlates with tumor aggressiveness, suggesting that it may play an important role in tumor growth. Recent evidence suggests that HER-2/neu may be a potential candidate for targeted immune intervention. In this report we show that cytotoxic T lymphocytes (CTL) expanded from tumor-associated lymphocytes with HLA-A2+ and HER-2/neu+ tumors can specifically recognize synthetic peptides corresponding to amino acids 971-980 of HER-2/neu protein. This sequence includes a potential amphiphilic area containing both Rothbard's epitode motifs and HLA-A2 anchor residues. Our study provides the first direct evidence of HER-2/neu-reactive CTL in humans. The fact that these HER-2/neu peptide-reactive CTL show significantly lower reactivity with corresponding EGF-R peptides offers new perspectives for understanding the recognition of self-antigens by tumor-reactive T cells.
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PMID:Cytotoxic T cells isolated from ovarian malignant ascites recognize a peptide derived from the HER-2/neu proto-oncogene. 769 18

Cell kinetics is a predictive parameter of breast-cancer aggressiveness, and mutations occurring in mammary tumorigenesis may favor uncontrolled cell proliferation. In this study, cell kinetics, clinico-pathological characteristics and genetic alterations at the int-2, bcl-1, c-myc, c-erbB-2, and DF3 loci were analyzed and correlated in 54 primary breast carcinomas. The occurrence of mutations at more than one locus was also studied. Tumor-proliferative activity was evaluated by determination of the thymidine labeling index (TLI). Amplification (AMP) of int-2 was observed in 11.2%, of bcl-1 in 9.4%, of c-myc in 5.7% and of c-erbB-2 in 8.6% of the carcinomas. Loss of heterozygosity (LOH) at the DF3 locus was detected in 13.9% of the tumors. Genetic alterations demonstrated a significant association with patient's age and high TLI values. AMP and LOH+AMP did not appear to be statistically related to histotype, histological grade, tumor size or lymph-node status. Alone, allele loss at the DF-3 locus was not significantly associated with any of the clinico-pathological characteristics studied. Alterations at more than one locus, including int-2/bcl-1, int-2/c-myc, int-2/bcl-1/c-erbB-2, and c-myc/DF3, were detected in 11.1% of the tumors. Multiple mutations were found only in less differentiated tumors, which included the 2 cases from the youngest patients of the series.
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PMID:High cell kinetics is associated with amplification of the int-2, bcl-1, myc and erbB-2 proto-oncogenes and loss of heterozygosity at the DF3 locus in primary breast cancers. 770 20

The EGF stimulation system for growth regulation is implicated in normal and neoplastic cell proliferation. The role of EGF, the EGF receptor, and c-erbB-2 in human gastric cancer is reviewed on the basis of several reports, which have been mainly oriented toward their clinical significance. EGF has been shown immunohistochemically to be present in 26% of gastric cancers (n = 395). The presence of EGF in gastric cancer is correlated with the degree of gastric wall invasion and lymph node metastasis. The 5-year survival of patients with EGF-positive tumors is worse than that of patients with EGF-negative tumors. The presence of EGF in human gastric cancer may therefore represent a higher malignant potential. Fifteen percent of gastric cancers (n = 352) were also shown to be positive for both EGF and the EGF receptor immunohistochemically, and the simultaneous occurrence of EGF and the EGF receptor suggests that these tumors grow in an autocrine fashion. Tumors exhibiting EGF and the EGF receptor simultaneously show a greater degree of local invasion and lymph node metastasis. Increased expression of EGF receptor protein in gastric cancer appears to be related to biologic aggressiveness, although gene amplification has occurred only to a small extent. Twelve percent of gastric cancers (n = 486) were found to be positive for c-erbB-2. This type of tumor has a frequent metastasis, and patients with c-erbB-2-positive cancer have a poorer prognosis than those with c-erbB-2-negative tumors. Selective blockade of the EGF receptor and c-erbB-2 from their ligands with monoclonal antibodies (MoAbs) inhibits the growth of human gastric cancer xenografts. These MoAbs may therefore be effective antitumor agents against gastric cancer showing overexpression of EGF receptors or c-erbB-2.
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PMID:Clinical significance of epidermal growth factor (EGF), EGF receptor, and c-erbB-2 in human gastric cancer. 788 68

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


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