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 administration of neoadjuvant chemotherapy to breast cancer (BC) patients with operable disease allowed studies aimed of exploring the interaction between cytotoxic treatment and tumour biology in vivo. 99 patients with T2-4, NO-1, M0 primary BC received a median of 3 cycles of either CMF regimen (cyclophosphamide, methotrexate, 5-fluorouracil) or single agent epirubicin. Endocrine therapy was also concomitantly administered in the first 45 patients with estrogen receptor positive (ER+) BC. 92 ended the treatment plan. Ki67 labelling index, estrogen receptor (ER), progesterone receptor (PgR), and c-erbB-2 oncoprotein expression were evaluated immunohistochemically in tumour biopsies obtained before and after chemotherapy. At post-chemotherapy evaluation, tumour shrinkage greater than 50% was obtained in 71 patients (79.7%), 27 of them being complete responders (30.3%). The median Ki67 labelling index, which was 13% in the first biopsy, decreased to 4.5% (p < 0.001) upon mastectomy. No significant differences were observed in steroid hormone receptor and c-erbB-2 expression before and after neoadjuvant treatment. In conclusion, neoadjuvant chemotherapy, whether associated or not to endocrine therapy, leads to a significant decrease in BC proliferation without any appreciable impact on c-erbB-2 and steroid hormone receptor expression.
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PMID:Effect of neoadjuvant chemotherapy on Ki67 labelling index, c-erbB-2 expression and steroid hormone receptor status in human breast tumours. 892 Jul 76

Using a polyclonal antibody against the c-erbB-2 gene product, an immunohistochemical study on the expression of c-erbB-2 oncoprotein was performed in routine formalin-fixed, paraffin-embedded tissue sections from 119 patients with primary breast cancer. Overexpression of c-erbB-2 protein was detected in 35 cases (29%). There was a strongly negative association between c-erbB-2 protein overexpression and estrogen receptor status (p < 0.001). Expression of c-erbB-2 protein was found to be related to clinical stage and tumor size (p < 0.05) but not to the number of involved nodes or age of patients at diagnosis. In addition, this study demonstrated that the c-erbB-2 protein over-expression was an effective independent prognostic indicator in patients with breast cancer.
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PMID:Immunohistochemical detection of c-erbB-2 oncoprotein in patients with breast cancer. 899 10

Before planning therapeutic strategies for patients at different risks of relapse, it is essential to identify prognostic factors. In addition to important anatomo-pathological prognostic factors such as lymph node status and tumour size, certain biological indicators, such as receptor status and proliferative kinetics, are now regarded as useful tools for prognosis. Tumour cell kinetics is an important prognostic variable in different stages of breast cancer. It is also a useful index for identifying subjects of aggressive tumours in node-negative patients. As far as the relationship between TLI estrogen receptor status and tumor size is concerned, it has been observed that only TLI retains its prognostic significance as regards both time to relapse and overall survival. Lymph node status, receptor status, cell kinetics and c-erbB-2 expression were examined as predictive factors of response. It emerged that not all chemotherapeutic regimens have the same impact in a situation where the disease is evaluated exclusively on the basis of lymph node status. Moreover, receptor status and receptor level significantly condition the response to endocrine therapy. Response rates to chemotherapy increase in highly proliferating tumours, whereas endocrine therapy achieves a better response in ER+ tumours with a low TLI index. Further studies are needed to clarify the role of c-erbB-2 as a predictive factor of response.
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PMID:[Role of biological indicators in the therapeutic decision in breast carcinoma]. 900 27

In a prospective pilot study, we performed breast fine needle aspirations (FNAs) on 213 high-risk and 30 low-risk women and analyzed these aspirates for cytologic changes and biomarker abnormalities of aneuploidy and overexpressed estrogen receptor (ER), epidermal growth factor receptor (EGFR), p53 and HER-2/neu. High-risk women were those with a first degree relative with breast cancer (73%), prior biopsy indicating premalignant breast disease (26%), a history of breast cancer (13%), or some multiple of these risk factors (11%). Median ages of the high-risk and low-risk groups were 44 and 42, respectively. Sixty-three percent of the high-risk and 73% of the low-risk group were premenopausal. Sixty-eight percent of the high-risk and 17% of low-risk women had cytologic evidence of hyperplasia with or without atypia (P < .0001). Aneuploidy and overexpression of EGFR and p53 occurred in 25%, 36%, and 28% of high-risk subjects but in less than 4% of low-risk subjects (P < .0002). Overexpression of ER and HER-2/neu occurred in 8% and 19%, respectively of high-risk women; nc low-risk women had these abnormalities. Sixty-eight percent of high-risk women and 7% of low-risk women had abnormalities of one or more of these biomarkers exclusive of cytology. Thirty-one percent of high-risk women, but no low-risk women had abnormalities of two or more biomarkers (P = .0004). Biomarker abnormalities were more frequent with increasing cytologic abnormality. Eighteen percent of women with normal cytology, 29% of women with epithelial hyperplasia and 60% of women with hyperplasia with atypia had abnormalities of two or more biomarkers (P = .048 and < .0001, respectively). Restricting the analysis to those three biomarkers most frequently overexpressed in the high-risk group (ploidy, EGFR, p53), 13% of high-risk women with normal cytology, 20% of high-risk women with epithelial hyperplasia and 51% of high-risk women with atypical hyperplasia had abnormalities of 2 or more of these 3 biomarkers. At a median follow up of two years, 8 of 213 women have been diagnosed with in situ (n = 5) or invasive (n = 3) cancer. Later detection of neoplasia was associated with prior FNA evidence of atypical hyperplasia (P < .0001) and multiple biomarker abnormalities in the 5 test battery (P = .006) by univariate analysis. By multivariate analysis, development and/or detection of cancer was primarily predicted by atypical hyperplasia (P = .0047) and secondarily by multiple biomarker abnormalities (P = 0.021). Atypical hyperplasia, EGFR, and p53 in breast FNAs have promise as risk markers and as surrogate endpoint biomarkers for breast cancer chemoprevention trials.
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PMID:Identification of a chemoprevention cohort from a population of women at high risk for breast cancer. 902 7

The proliferative activity of 30 cases of non-treated invasive ductal breast carcinoma was evaluated by bromodeoxyuridine (BrdU), proliferation marker (MIB-1) and proliferating cell nuclear antigen (PCNA), and the relation between these proliferation markers and histological subtype and histological grade were investigated. In addition, the association of these proliferation markers with overexpression of p53 protein, c-erbB-2 oncoprotein, estrogen receptor (ER) status and clinicopathologic findings were also examined. The BrdU labeling index (LI), MIB-1 score and PCNA labeling rate (LR) correlated with the histological grade. However, there was no statistical difference in proliferative activity among the histological subtypes. A linear strong correlation was demonstrated between BrdU LI and MIB-1 score (r = 0.732). Significant correlation was also found between BrdU LI and PCNA LR (r = 0.446); however, the relation between MIB-1 score and PCNA LR was weak. BrdU LI and MIB-1 score correlated positively with tumor size, TNM stage and overexpression of p53, and negatively with the presence of ER. PCNA LR correlated only with p53. These results indicate that MIB-1 is closely associated with BrdU in clinicopathologic findings and is a more useful tool for evaluating cell proliferation than PCNA. However, it will be necessary to consider the clinical significance of MIB-1 immunohistochemistry cautiously until further widespread clinical and pathological studies are performed.
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PMID:Proliferation marker MIB-1 correlates well with proliferative activity evaluated by BrdU in breast cancer: an immunohistochemical study including correlation with PCNA, p53, c-erbB-2 and estrogen receptor status. 911 Mar 47

We have performed immunohistochemical staining for p53 and c-erbB-2 on formaldehyde-fixed, paraffin-embedded primary invasive ductal carcinomas from 112 patients, with a minimal follow-up time of 60 months. All of them had received postoperative chemoradiation therapy. We have analyzed the association of these factors with epidemiologic risk factors, histopathologic features and hormonal receptor status and the influence on prognosis. Our results indicate that the expression of c-erbB-2 protein defines a group of node-negative patients with poor prognosis. The overexpression of c-erbB-2 has shown a significant association with estrogen receptor status (those tumors expressing c-erbB-2 are usually estrogen receptor negative), presence of fibrosis and lymphoplasmacytoid infiltrates. P53 expression has shown no relation either with prognosis or with any other histopathologic or clinical feature. The only factors with prognostic influence in our series have been tumor size, the presence of node metastases, TNM stage and the prognostic morphometric index (Baak's index), apart from c-erbB-2 in node-negative patients. However, only the TNM stage showed an independent association with prognosis after a multivariate analysis. In summary, in our experience the expression of p53 protein has no prognostic influence on breast carcinoma, and TNM stage remains to be as the most powerful prognostic factor in these patients.
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PMID:Immunohistochemical expression of p53 and c-erbB-2 in breast carcinoma: relation with epidemiologic factors, histologic features and prognosis. 922 51

HER-2/neu and c-myc amplification or overexpression have been reported to be associated with poor prognosis in breast carcinoma. The prognostic significance, however, remains somewhat controversial, partly because of discrepancies among different methodologies used for detection of the oncogene amplification or overexpression. Fluorescence in situ hybridization (FISH) has recently been shown to be a useful technique for analyzing genetic alterations in interphase nuclei in various tumors. In this study, FISH was used to quantitate HER-2/ neu and c-myc gene amplification in touch preparations of frozen tissue from 100 node-negative breast carcinomas. HER-2/neu amplification was found to be associated with an abnormal DNA index (P < .001) and tumor size (P < .04). Amplification of c-myc was associated with S phase (P < .0003), abnormal DNA index (P < .003), and a negative estrogen receptor status (P < .01). The coamplification of both oncogenes was strongly associated with an abnormal DNA index (P < .0001) and with tumor size (P < .009). The use of FISH for detection of HER-2/neu gene amplification was 92% concordant with immunocytochemistry (ICC) used for detection of overexpression of HER-2/neu protein. Fifteen of the 100 cases were both amplified for HER-2/neu by FISH and positive by ICC analysis. Seven cases without HER-2/neu gene amplification demonstrated HER-2/neu protein overexpression by ICC. One HER-2/neu-amplified case was negative by ICC. Repeat analysis of a subset of cases showed FISH to be a more reproducible method than ICC in the analysis of HER-2/neu in touch preparations of breast carcinoma. FISH is a rapid and reproducible method that allows the accurate measurement of the level of oncogene amplification within interphase nuclei. The use of FISH should provide a more accurate assessment of the prognostic significance of oncogene amplification in breast carcinoma.
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PMID:Quantitation of HER-2/neu and c-myc gene amplification in breast carcinoma using fluorescence in situ hybridization. 923 84

Angiogenesis is essential for tumour growth and metastasis. In spite of its relevant biological significance, recent studies have produced conflicting results regarding the capacity of microvessel quantifications in breast carcinomas to predict patients' outcome and the existence of metastasis. In order to provide further information in this issue, we evaluated tumour angiogenesis in a series of 45 primary breast carcinomas (mean age: 55.3 +/- 14.2) and examined their association with established or potentially useful prognostic parameters. Microvessels were highlighted by immunohistochemical staining for factor VIII-related antigen and counted in the three most vascularized areas in a 200 x field (0.74 mm2) by four observers simultaneously. Results were analysed for the average vessel count of each case. The mean intratumoural microvessel count was 57.7 +/- 24.4 (range: 24.3 to 127.7). We found a statistically significant association between angiogenesis and age. The microvessels count in patients younger than 50 years was 67.8 +/- 26.4, from 51 to 70 years, 52.0 +/- 22.8 and over 71 years, 46.1 +/- 14.2 (p = 0.03). Node positive patients had slightly higher microvessel counts (60.3 +/- 25.3) than node negative ones (54.4 +/- 23.5); this difference was not significant (p = 0.42), even when we considered each age group per se. No association was found between angiogenesis and tumour size, histologic grade, estrogen receptor, MIB-1 index, ploidy and expression of p53 and c-erbB-2. Our results suggest that invasive breast carcinoma-induced angiogenesis is age-dependent.
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PMID:Angiogenesis in breast cancer is related to age but not to other prognostic parameters. 925 52

Amplification of erbB-1 and c-erbB-2 genes has been shown in human breast cancer. Expression of these protooncogenes results in production of epidermal growth factor receptor (EGFR) and c-erbB-2. Both are transmembrane receptors with tyrosine kinase activity. Recent data have indicated that the external domain of c-erbB-2 is shed into the culture supernatant of certain breast cancer cell lines and sera of breast cancer patients. A body of literature has shown that the overexpression of these receptors in malignant tissue and c-erbB-2 when shed into serum is associated with bad prognosis. In the present work, tissue EGFR and c-erbB-2 were determined in the membrane fractions of histopathologically verified malignant and normal tissues from the same breast of 94 patients. These values were also determined in 48 tissue specimens of benign mastopathies. Serum c-erbB-2 was quantified in breast cancer patients (n = 105), patients with benign breast disease (n = 48) and 30 apparently healthy women as controls. Patients were followed up by determination of serum c-erbB-2 for one year and clinically for three years to detect any distant metastasis or recurrence. The levels of tissue and serum c-erbB-2 and Estrogen receptors were significantly higher in the carcinomas and sera of breast cancer patients than benign breast diseases or normal controls. Follow-up, although short, of pre-operative serum c-erbB-2 showed a prognostic value (P = 0.007) better than that of tumor size (P = 0.04), EGFR (P = 0.18), nodal involvement (P = 0.25) and tissue c-erbB-2 (P = 0.85). The shedding of soluble fragments of c-erbB-2 into the serum seems to be a characteristic of the potentially malignant cell. The EGFR mean level, however, was significantly lower in malignant tissues than benign and normal ones. A new definition of EGFR status was developed. Accordingly, the recurrence of the disease was more frequent among patients with negative EGFR. The present work did not reveal any correlation between tissue, serum c-erbB-2 or EGFR on one hand and age, menopausal status, stage, histological type and grade of carcinomas and nodal involvement on the other hand. The present work showed an inverse correlation between estrogen receptor level and level of EGFR in malignant tissues.
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PMID:Tissue and serum c-erbB-2 and tissue EGFR in breast carcinoma: three years follow-up. 932 11

Morphologic mimicry among human malignant neoplasms is a well-known phenomenon in surgical pathology; both undifferentiated and "committed" neoplasms may exhibit this trait. One particularly common group of histologic simulants includes ductal carcinomas of the breasts, the cutaneous appendages, and the salivary glands. One hundred three tumors in this structural cluster were analyzed microscopically and immunohistologically to codify points of potential pathologic similarity and difference. All the lesions were typified by irregularly permeative clusters and cords of atypical polygonal cells with variable luminal differentiation. A proportion of primary neoplasms in each site demonstrated in situ ductal components; in the absence of the latter elements, however, it was not possible to make topography-related morphologic distinctions among them. Immunostains for gross cystic disease fluid protein-15 (GCDFP-15), carcinoembryonic antigen, S100 protein, c-erbB-2 oncoprotein, estrogen receptor protein, and progesterone receptor protein also showed largely overlapping phenotypes in each of the three tumor categories, with selected exceptions. These differences were elucidated through paired chi 2 analysis and included a statistically significant infrequency of GCDFP-15 in eccrine sweat gland carcinomas, a paucity of carcinoembryonic antigen in breast cancers, and an absence of estrogen receptor protein in salivary duct carcinomas. Such findings may be useful in predefined differential diagnostic settings involving the distinction between primary and metastatic ductal cancers of the breasts, skin, and salivary glands. Nevertheless, because of the striking homologies between such tumors at structural and protein-synthetic levels of comparison, it is mandatory that all available clinicopathologic information be used in this context.
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PMID:Homologous carcinomas of the breasts, skin, and salivary glands. A histologic and immunohistochemical comparison of ductal mammary carcinoma, ductal sweat gland carcinoma, and salivary duct carcinoma. 1023 Mar 63


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