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 breast cancer patients, prognostic information required to plan post-surgical therapy is obtained mainly through axillary dissection. This study was designed to establish a new prognostic score based solely on parameters of the primary tumour as an alternative to axillary surgery in assessing prognosis. Eight different prognostic factors, including menopausal status, tumour size, grading, lymphatic invasion, desmoplasia, necrosis, c-erbB-2 and laminin receptor expression, were evaluated retrospectively on a large series of primary breast carcinoma patients. From multivariate analysis, four independent parameters were selected and examined, alone and in combination, for their prognostic potential. These parameters were used to generate a prognostic score that was analysed retrospectively in 467 N0-N1a patients to determine its predictive value for survival. The score, which includes variables such as tumour size, grading, laminin receptor and c-erbB-2 overexpression, was established based on the number of negative prognostic factors: score 1 refers to cases in which all four parameters reflect a good prognosis, scores 2 and 3 refer to tumours in which, respectively, one or two of the four parameters reflect a poor prognosis, whereas score 4 refers to tumours with three or four poor prognosis factors. Analysis of the overall survival of the four score groups shows that patients with score 1 tumours (22% of the total) had the best prognosis with a 15 year survival of 82%, patients with score 2 and 3 had an intermediate prognosis, whereas score 4 patients had the poorest prognosis with a 15 year survival of only 38%. Moreover, survival in the N+ score 1 cases was found to be longer than that in the total N- patients. Our data suggest that the primary tumour score provides more reliable prognostic information than pathological nodal status, and that axillary dissection can be avoided in a large number of patients.
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PMID:Prognosis based on primary breast carcinoma instead of pathological nodal status. 791 24

152 curative gastrectomy specimens from patients with gastric carcinoma were examined in an attempt to assess the prognostic value of c-erbB-2 and mutant p53 protein expressions. The labeled streptavidin-biotin method was applied to routinely fixed and paraffin-embedded tissue sections, using the polyclonal and monoclonal antibodies against the c-erbB-2 protein and the mutant form p53 protein, respectively. In this examination, staining of c-erbB-2 protein was found in 9.2% of these carcinomas. The c-erbB-2 stained tumors were significantly associated with the tumors whose diameters were smaller than 5cm, and were more likely to be associated with serosal invasion and nodal involvement than the unstained ones. However, there was little association between staining of c-erbB-2 protein and clinicopathologic findings such as age, sex, location, histology, gross type, lymph node status, depth of invasion, and stage. The survival analysis of 104 patients with stage III gastric carcinoma revealed no significant association between c-erbB-2 staining status and survival duration. The 5-year survival rates of the c-erbB-2 positive group and its negative group were 21% and 28%, respectively. Positive p53 protein expression was observed in 46% of 152 carcinomas. There was no significant association between p53 expression and parameters such as age, sex, location, histology, gross type, and size. The p53 stained tumors were more likely to be associated with lymph node metastasis, serosal invasion than p53 unstained ones; but this did not reach significance. The 5-year survival rates of the p53 positive group and counter part group were 27% and 31%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The prognostic significance of c-erbB-2 and p53 protein expressions in gastric carcinoma--a multivariate analysis of prognostic factors. 799 93

In order to clarify the clinical significance of mutations of the p53 gene and amplification of the c-erbB-2 gene in breast carcinoma, these gene alterations were examined in 101 invasive, seven predominantly intraductal and 10 intraductal breast carcinomas by single-strand conformation polymorphism-direct sequencing or Southern blot-hybridization analysis. p53 mutations were detected in 32 (32%) of the invasive cases and two (12%) of the 17 intraductal/predominantly intraductal cases, whereas c-erbB-2 amplification was detected in 14 (14%) of the invasive and six (35%) of the intraductal/predominantly intraductal cases. Irrespective of differences in the positions and types of the mutations, cases carrying p53 mutations were almost always Grade 3 histologically and with a low hormone-receptor value. Since p53 mutations as well as c-erbB-2 amplification were detected almost selectively in Grade 3 cases but were not associated with lymph nodal status in invasive breast cancer, these two gene alterations could be indicators of prognosis of disease independent of lymph nodal status. Even in intraductal/predominantly intraductal carcinoma, these gene alterations were almost always detected in tumors of higher histologic grade. Thus, it is suggested that these gene alterations occur in breast cancers showing a high proliferation rate irrespective of the presence of invasion, and that other molecular alterations are involved in the process of breast cancer invasion.
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PMID:p53 mutations and c-erbB-2 amplification in intraductal and invasive breast carcinomas of high histologic grade. 809 3

If axillary lymph node metastases were able to be accurately predicted, dissection could be avoided in some patients with breast cancer whose axillary nodes are clinically negative. In this study, we assessed the relationships between histological axillary lymph node metastases and clinical axillary nodal status, tumor size, DNA-ploidy, c-erbB-2 expression, and the score of the argyrophilic nucleolar organizer region. We then attempted to evaluate their predictive values for axillary lymph node metastasis in 173 patients with invasive breast cancer, retrospectively. The clinical and biological variables were significantly correlated with the presence and degree of axillary lymph node metastases. A metastatic index, calculated from the clinical and biological variables, proved especially useful for predicting axillary lymph node metastases in patients whose axillary nodes were clinically negative. However, the predictive abilities were still limited and thus it was concluded that as yet, only axillary dissection can provide accurate information on axillary lymph node metastases.
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PMID:A retrospective study on the clinical and biological prediction of axillary lymph node metastasis in breast cancer. 810 89

Among 843 cases of breast cancer, p53 oncoprotein was detected by the monoclonal antibody (MoAb) Pab-1801 in only 13%. Low-grade carcinomas (tubular, mucinous, papillary, and invasive cribriform types) did not express p53 protein, but it was observed in 4.2% of infiltrating lobular carcinomas (6 of 140 cases) and 50% of pure medullary carcinomas (5 of 10 cases). In intermediate-grade neoplasms, no correlation was seen between p53 status and other putative determinants of a poor prognosis. The latter included high tumor stage, lymph nodal involvement, high growth fraction (as determined by labeling with the MoAb Ki-67), negative results for estrogen receptor (ER) and progesterone receptor (PR) proteins, and amplification of the c-erbB-2 oncogene product in the neoplastic cells. Ninety-nine of 640 (15.5%) cases of high-grade, invasive, ductal breast carcinoma, however, showed an inverse relationship between expression of p53 protein and positive results for ER/PR proteins and a direct correlation with large tumor size, Ki-67-determined growth fraction, and amplification of c-erbB-2 oncopeptide. All of the latter associations were highly significant statistically. The authors conclude that mutant p53 protein may serve a prognostic role in a subset of cases of invasive ductal mammary carcinoma.
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PMID:Relationship between p53 expression and other prognostic factors in human breast carcinoma. An immunohistochemical study. 837 28

Human solid tumors accumulate multiple genetic abnormalities as they progress to advanced stages. Multiparameter flow cytometry measurements of individual cells within each tumor may be useful in describing the genetic pathways taken by individual tumors during the course of their genetic evolution. In this paper, we analyzed correlated cell-by-cell measurements of cell DNA content, HER-2/neu protein content, and ras protein content obtained by multiparameter flow cytometry studies of primary breast cancers from 92 patients. These laboratory findings were correlated with established clinical prognostic factors for each patient at the time of diagnosis, using a stepwise multiple analysis of variance (MANOVA). The stepwise MANOVA successively splits a group of patients into two mutually exclusive dissimilar groups, selecting the clinical prognostic factor that is most effective in doing so. Using this criterion, formation of the first three groups that were judged most dissimilar on the cytometry parameters was based on the number of positive nodes at the time of diagnosis. We show that ploidy, HER-2/neu protein content, and ras protein content, as measured by multiple parameter flow cytometry, are correlated with nodal status and other known clinical prognostic factors. The cell-by-cell multiparameter data suggest that for some individual tumors there are multiple genetic evolutionary pathways. Multiple genetic evolutionary pathways are also suggested by the MANOVA analysis. Focusing on the identification and analysis of genetic evolutionary pathways within individual tumors and across patients appears to offer a promising approach for defining the prognosis of early cancers.
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PMID:Analytical approaches relating genetic evolutionary pathways to prognostic factors. 852 67

The role of molecular markers predicting the response to cytotoxic chemotherapy is not established. A potential predictive factor, topoisomerase IIalpha, is a target for certain cytotoxic drugs, and its concentration has been shown to correlate with chemosensitivity in vitro. We evaluated expression of topo IIalpha immunohistochemically in 230 breast cancer samples and studied its association with known clinicopathological factors and factors previously shown to predict response to cytotoxic drugs. Topo IIalpha protein expression was found in 0.6 to 39.4% (10.6 +/- 7.9%, mean +/- SD) of breast carcinoma cells, whereas expression was undetectable in nonmalignant breast epithelium. Topo IIalpha protein expression correlated well with semi-quantitative mRNA in situ hybridization (P = 0.007). A significant association was found between the proportion of topo-IIalpha-positive cells and low estrogen and progesterone receptor content (P<0.0001), high grade (P<0.0001), DNA aneuploidy (P=0.003), and c-erbB-2 oncoprotein overexpression (P<0.0001). Topo IIalpha expression was not associated with clinical variables, such as age of the patient, primary tumor size, or axillary nodal status. A highly significant linear correlation was found between topo IIalpha and tumor proliferation rate (S-phase fraction, r=0.46; P<0.0001). Because hormone receptors, grade, and ploidy are associated with tumor proliferation rate, topo IIalpha expression was adjusted for S-phase fraction to reveal the proliferation-independent clinopathological associations. According to the analysis of co-variance, only aneuploidy (P=0.0003) and c-erb-2 overexpression (P=0.01) were associated with proliferation-adjusted expression of topo IIalpha. In conclusion, the close association of Topo IIalpha with other potential predictive factors (tumor proliferation rate, c-erbB-2 oncoprotein) suggests that topo IIalpha, having a defined role as a target for cytotoxic drugs, may be a valuable predictor of response to chemotherapy.
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PMID:Expression of topoisomerase IIalpha is associated with rapid cell proliferation, aneuploidy, and c-erbB2 overexpression in breast cancer. 866 91

The immunohistochemical expression of p53 and c-erbB-2 gene proteins was examined in a series of 130 breast adenocarcinomas. This study intended to investigate whether the frequency of the altered expression of the tumour suppressor gene p53 and the overexpression of the oncogene c-erbB-2 in breast cancer tissue cells correlated with other variables known to affect the biological behaviour of these tumours and the overall survival of the patients (median follow-up time: 6 years). The expression of p53 protein and c-erbB-2 gene product was evaluated immunohistochemically. Expression of p53 protein was detected in 30 (23 per cent) of the neoplasms examined, while 26 (20 per cent) out of the 130 cases demonstrated positive c-erbB-2 immunoreactivity. There was a statistically significant association between p53 protein expression and primary tumour size, lymph node involvement, and oestrogen receptor positivity. The incidence of c-erbB-2 positivity was significantly correlated with high tumour grade, axillary node invasion, large tumour size, and the absence of steroid receptors. p53 immuno-expression was clearly associated with c-erbB-2 protein overexpression. Concomitant p53 and c-erbB-2 positive immunolabelling, which emerged in 14 out of the 130 cases (10.7 per cent), was clearly associated with high grade, large size, positive nodal status, ductal infiltrating (NOS) histological type, and low values of progesterone receptors. Overall survival of patients was not significantly related to the immunoreactivity of either p53 or c-erbB-2 considered separately, whereas there was a clearly significant trend to worse overall prognosis in cancers with double p53/c-erbB-2 positive phenotype. The simultaneous immunodetection of p53/c-erbB-2 appears to have greater negative prognostic relevance than their separate expression.
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PMID:Prognostic significance of the co-expression of p53 and c-erbB-2 proteins in breast cancer. 869 41

C-erbB-2 serum levels were studied in the sera of 50 healthy subjects, 56 patients with benign breast diseases and 412 patients with breast cancer. Using 15 U/ml as the cut-off, no healthy subjects, patients with benign disease and only 2.4% of patients with no-evidence of disease had serum levels higher than this cut-off point. Abnormal c-erbB-2 levels were found in 9.2% of the patients with locoregional breast carcinoma and in 45.4% of those with advanced disease. C-erbB-2 serum levels in patients with locoregional breast cancer were not related to tumor size or nodal involvement. By contrast, significantly higher c-erbB-2 serum levels were found in ER- or PgR- tumors than in those ER+ or PgR+ tumors, in both locoregional or metastatic tumors. The correlation between serum and tissue levels of C-erbB-2 was studied in the tumors of 161 patients. Significantly higher c-erbB-2 serum levels were found in patients with overexpression in tissue by immunohistochemistry, in both locoregional and advanced disease (p = 0.0001). In patients with C-erbB-2 overexpression in tissue, c-erbB-2 serum levels were related to tumor size and nodes, with higher values in tumors greater than 5 cm or in those with more than 3 nodes involved. When the prognostic value of this oncoprotein was evaluated, patients with abnormally high presurgical c-erbB-2 had a worse prognosis than those patients with normal values, in both node-negative and node-positive patients. Serum concentrations in patients with advanced disease, were related to the site of recurrence with significantly higher values in patients with metastases (mainly in those with liver metastases) than in those with locoregional recurrence. In summary, c-erbB-2 serum level seem to be a useful tumor marker in the prognosis of patients with breast cancer.
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PMID:C-erbB-2 oncoprotein in the sera and tissue of patients with breast cancer. Utility in prognosis. 869 59

We examined 232 breast carcinomas for c-erbB-2 amplification by Southern analysis using two different cDNA probes. Using these same probes, 95 of these tumors were also examined for mRNA expression by Northern analysis. Amplification was detected in 20 and 17% of the tumors with the probes pHER 2 and pCER 204, respectively, but only 10% showed amplification with both probes. A significantly higher incidence (p < 0.01) of mRNA overexpression was detected with the pHER 2 probe (34%) compared with the pCER 204 probe (16%), with only 11% of tumors demonstrating overexpression with both probes. A total of 10 tumors (11%) exhibited amplification as well as overexpression with pHER 2, whereas significantly fewer (3%) manifested both abnormalities with the larger pCER 204 probe (p < 0.05). Amplification of c-erbB-2, as detected with the pHER 2 probe but not with the pCER 204 probe, was significantly associated with the absence of both estrogen and progesterone receptors (p < 0.05 and p < 0.01, respectively). No relationship was found with other clinical prognostic indicators, such as nodal involvement and metastases. As determined by either probe, overexpression was not associated with prognostic indicators. There was no significant difference in the c-erbB-2 status of tumors from different racial groups.
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PMID:Variations in c-erbB-2 proto-oncogene status in breast cancer tumors as detected by two different cDNA probes. 886 31


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