Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The c-myc proto-oncogene was analyzed in 311 cases of primary breast cancer, in 8% of which it was found to be amplified, usually at moderately increased copy number (2-5 copies). The adjacent pvt gene was co-amplified with c-myc in all tumors analyzed. C-myc amplification was significantly correlated to a high S-phase fraction and to amplification of the c-erbB-2 proto-oncogene. Weak relationships were found between c-myc amplification and the presence of lymph-node metastasis, advanced stage, DNA non-diploidy and premenopausal status, but not tumor size, estrogen receptor or progesterone receptor status, or int-2 amplification. C-myc amplification, and especially a high gene copy number (greater than 5 copies), was significantly related to early recurrence and death in breast cancer, a relationship seen in both the lymph-node-negative and node-positive subcategories. A particularly strong correlation with poor clinical outcome was seen in postmenopausal patients (p greater than 0.0005), an association which persisted in multivariate survival analysis. We conclude that the activation of c-myc is indeed associated with rapidly growing and progressive breast cancer. Gene amplification, on the other hand, is relatively infrequent and occurs mostly at low copy number, implying that tumors are heterogeneous with respect to cell clones harboring c-myc amplification. An immunohistochemical assessment would more accurately illustrate the importance of c-myc activation in human breast cancer. However, the obvious instability of the c-myc transcript and translate suggests that c-myc is not a suitable prognostic marker for routine purposes.
 ...
PMID:c-myc amplification is an independent prognostic factor in postmenopausal breast cancer. 161 75

Human breast cancer cell proliferation is regulated by growth factors that bind to receptors with intrinsic tyrosine kinase (TK) activity, including the epidermal growth factor (EGF) receptor. To determine whether inhibition of receptor TK activity inhibits tumor growth, we studied the effects of a tyrosine kinase inhibitor, RG-13022, on cultured human breast cancer cells. RG-13022 represents a class of compounds which have been shown to inhibit preferentially the TK activity of the EGF receptor in a cell-free system and also to inhibit EGF-stimulated growth of cultured cells. RG-13022 significantly inhibited EGF-stimulated autophosphorylation of its receptor in two breast cancer cell lines that have abundant, although not amplified, EGF receptor content (MDA-231 and T47D). RG-13022 also inhibited EGF-stimulated DNA synthesis and proliferation of T47D and MCF-7 breast cancer cells in a reversible and dose-dependent manner. Inhibition was observed at 0.1 microM, and it was maximal at 10 microM. The effect was rapid (within 3 h), persisted for 18 h, and was partially reversed by 24 h at 1 microM. At 5 microM, inhibition persisted for more than 50 h. Inhibitory effects were also observed in a panel of estrogen receptor-positive and estrogen receptor-negative breast cancer cell lines. RG-13022 inhibited not only EGF-induced growth but also growth stimulated by insulin, insulin-like growth factor I, insulin-like growth factor II, or transforming growth factor alpha. RG-13022 also totally blocked estrogen-stimulated phosphorylation of the EGF receptor, as well as estrogen-induced cell proliferation, suggesting that functioning TK pathways are required for estrogen action. The TK inhibitor RG-13022 is a potent inhibitor of hormonally regulated growth of human breast cancer. Tyrosine kinase inhibitors have the potential of providing a new strategy for the "endocrine therapy" of breast cancer.
 ...
PMID:Inhibition of breast cancer cell growth in vitro by a tyrosine kinase inhibitor. 161 36

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.
 ...
PMID:Correlation between c-erbB-2 amplification and risk of recurrent disease in node-negative breast cancer. 167 Jul 62

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.
 ...
PMID:Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease. 167 Sep 8

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.
 ...
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

An immunohistochemical study was performed on 211 primary breast carcinomas for c-erbB-2 expression. All patients had involvement of axillary lymph nodes and all were randomised onto one of the Ludwig Breast Cancer Trials I-IV between July 1978 and August 1981. c-erbB-2 overexpression significantly correlated with high S-phase fraction, four or more positive axillary nodes involved, estrogen receptor negative primaries, progesterone receptor negative primaries, high grade tumours and DNA aneuploidy. With a nine year median follow-up c-erbB-2 positive tumours had worse disease-free survival (p = 0.0002) and overall survival (p less than 0.0001). Multivariate analyses using proportional hazard regression models demonstrated that c-erbB-2 positivity continued to predict a poor outcome even when accounting for the effects of other prognostic factors.
 ...
PMID:Association of c-erbB-2 expression and S-phase fraction in the prognosis of node positive breast cancer. 167 97

Nucleolar antigen P120 is detected in rapidly proliferating cells but not in normal resting cells or in many benign and slowly growing malignant tumors. The objective of the study was to determine whether the expression of P120 in breast cancer correlated with histopathological or biological properties associated with prognosis. In this retrospective study, 120 primary breast tumors were analyzed for P120; 114 of these tumors were also stained for the erbB-2 protein. Immunopositive staining was correlated with patient survival, nodal status, estrogen receptor levels, and number of mitoses. Sixty-nine % (83 of 120) of the tumors were positive for P120; 25% (28 of 114) stained positively for erbB-2. Of the 28 erbB-2 positive tumors 26 were also positive for the P120 protein. Forty-six % (55 of 120) of the specimens were from patients who later died from recurrent breast cancer; P120 was detected in 89% (49 of 55) of these specimens. In 52% of the survivors the P120 protein was also expressed. P120 negative tumors were highly correlative with survival (P = 0.0001); 84% (32 of 37) of patients with P120 negative tumors survived more than 7 years without evidence of recurrent disease. Multivariate analysis showed that the worst prognosis was for patients who had tumor positive nodes and expressed P120 (P = 0.0001); death occurred in 73% (30 of 41) of these patients. For the node negative patients who did not express P120, 5-year survival was 90% (19 of 21 patients); 5-year survival for the node negative patients who expressed P120 was significantly less (67%; 28 of 42 patients). Patients with P120 negative tumors had a good prognosis, irrespective of their nodal status. In this group, survival of node negative patients was 86% (18 of 21) and for those with positive nodes survival was 82% (13 of 16). A poor prognosis was found for patients with intense erbB-2 stained tumors (5 of 7 patients died). Weak staining of erbB-2 tumors (21 specimens) was not correlated with patient survival. Compared to P120 negative tumors, P120 positive tumors had greater numbers of mitoses (9.06 versus 6.65) and an almost 2-fold increase in the occurrence of positive nodes (one of every 4.67 versus one of every 8.81). The number of P120 positive tumors was greater in estrogen receptor positive tumors (75%) than in estrogen negative tumors (54%).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Prognostic significance of proliferation associated nucleolar antigen P120 in human breast carcinoma. 167 21

We reviewed tumors from two groups of patients with breast cancer, distinguished by differences in outcome. One group (85 cases) survived more than 8.5 years without tumor recurrence; the other 85 cases had recurrent disease within 2 years. Histologic and immunocytochemical studies on all cases were performed without patient identifiers and prior to review of clinical prognostic factors. As expected, lymph node and estrogen receptor status differed substantially between the groups, but menopausal status and family history for breast cancer did not. We noted that 27% of node-negative patients died within 5 years, and nine patients with four or more tumor-containing nodes were symptom-free for over 8.5 years. Histologic grade (degree of tubule formation) and nuclear grade (including mitotic rate) differed significantly between the groups, as did vascular invasion, including both lymphatics and blood vessels. Prognostic value attached to tumor border only when fat was invaded without fibroblastic or inflammatory response (P = .012). Subgrouping cases of infiltrating ductal carcinoma (not otherwise specified) was prognostically informative in the B subgroup, 69% of whom were in the rapidly recurrent tumor group. Immunocytochemical staining for c-erbB-2 was positive in 19.3% of cases, but was equally distributed between the two outcome groups. We conclude that traditional histologic parameters are highly informative, and that c-erbB-2 studies do not increase the value of histologic diagnosis.
 ...
PMID:A retrospective analysis of breast cancer based on outcome differences. 167 93

Using the 21N polyclonal antibody, we immunohistochemically stained 314 primary breast carcinomas to identify those tumors overexpressing the c-erbB-2 oncoprotein and to ascertain the prognostic significance of this expression on disease-free and overall survival. Positive membrane staining was present in 52 (17%) of these carcinomas of which 7 (13%) were ductal carcinomas in situ. There was no significant relationship between c-erbB-2 positivity and (a) age at diagnosis, (b) menopausal status, (c) tumor size, (d) lymph node status, (e) estrogen receptor status, or (f) whether or not the patient had disseminated disease outside the axillary fields. However, c-erbB-2-positive tumors were significantly associated with poorer grade (P = 0.02). Patients who were positive for this oncoprotein had a shorter disease-free survival (P = 0.002) and reduced overall survival (P = 0.0001). Overexpression of this oncoprotein was predictive of a worse prognosis in lymph node-positive disease (P = 0.003) and in patients presenting with grade II tumors (P = 0.001). Stratifying the patients on the basis of estrogen receptor status suggested that c-erbB-2+/estrogen receptor-negative status was predictive of a poorer prognosis when compared with the other subgroups (P less than 0.001). Primary and recurrent tumor tissues were available from 42 of the 314 patients. Identical patterns of c-erbB-2 expression occurred in 95% of cases, arguing against a direct role for c-erbB-2 expression in the process of tumor dissemination. The high incidence of staining in ductal carcinomas in situ suggests that expression of this oncoprotein is an early event in tumorigenesis. Finally, multivariate analysis indicated that the c-erbB-2 oncoprotein was an independent prognostic indicator for overall survival in breast carcinoma patients.
 ...
PMID:Prognostic significance of c-erbB-2 and estrogen receptor status in human breast cancer. 167 98

The c-erbB-2 oncogene, is a member of tyrosine kinase oncogene family and expected to play a role in the regulation of cell growth. In the present study, prognostic significance of the expression of c-erbB-2 oncoprotein was investigated by immunocytochemical assay with 130 primary breast cancer patients. The positive expression of c-erbB-2 oncoprotein was found in 53 out of 130 patients (40.8%). There was no significant correlation between expression of c-erbB-2 oncoprotein and conventional prognostic factors, estrogen receptor (ER), axillary lymph node metastasis and epidermal growth factor receptor (EGFR). Relapse free survival rate of the patients with positive c-erbB-2 expression was significantly worse than those with negative at 49 month after operation. Similar result was found in overall survival rate but the difference was not significant. Furthermore, when patients were stratified by regional nodal status, in the patients with lymph node metastasis, the prognosis of the patients with positive c-erbB-2 expression was significantly worse than those with negative, while no significant difference was found in the patients without lymph node metastasis. These results suggest that c-erbB-2 oncoprotein may act as a prognostic factor independently, predicting the prognosis of breast cancer patients.
 ...
PMID:[Prognostic significance of expression of c-ERBB-2 oncoprotein in breast cancer patients]. 167 44


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>