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 follow-up study of 143 cases of human breast cancer for over 5 years proved that Her-2/neu oncogene overexpression is much more common in the high risk group (patients died within 5 years) in comparison with the low risk group (patients survived over 5 years). The difference between these 2 groups was statistically significant. The Her-2/neu oncogene positive rate in infiltrative ductal carcinoma was 33.3%, the lower the differentiation, the higher the positive rate. Histological typing is also related to the positive rate, comedocarcinoma (intraductal carcinoma) expresses the highest positive rate while lobular carcinoma the lowest. Selection of fixation fluid and the mastering of diagnostic criteria are also important. In the author's opinion, only membrane staining in monoclonal antibody C-erbB-2 can be recognized as truly positive. In conclusion, Her-2/neu oncogene expression can be used as a supplemental marker when considering prognosis in breast cancer.
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PMID:[Study of Her-2/neu oncogene in relation to prognosis of human breast cancer]. 790 1

To clarify whether p53 protein expression is involved in multistep carcinogenesis or the progression of mammary ductal carcinoma, we investigated p53 protein expression in 83 invasive ductal carcinomas (IDC), 10 IDC with a predominant intraductal component, 13 non-invasive ductal carcinoma (NIDC), 16 atypical ductal hyperplasia (ADH) and 39 benign epithelial hyperplasia (EH), using immunohistochemistry. Expression of p53 protein was detected in 24 (28.9%) cases of IDC, 5 (50%) cases of IDC with a predominant intraductal component and 1 (7.6%) case of NIDC. No expression was observed in either ADH or EH. In IDC, including cases with a predominant intraductal component, p53 protein expression was associated with a higher histological grade (P < 0.0001) or mitotic index (P < 0.0005). Although overexpression of c-erbB-2 protein has also shown a similar association with these prognostic indicators, expression of p53 protein correlated regardless of the status of c-erbB-2 overexpression. Completely coordinated expression of p53 protein was seen in both intraductal and invasive components. The intraductal component in IDC including cases with a predominant intraductal component which expresses p53 protein had significantly higher histological grade (P < 0.0005) or more comedo-subtypes (P < 0.0001). These results suggested that p53 protein expression occurs at a stage of NIDC with high histological grade or in comedo-subtypes. Its expression is maintained throughout invasion.
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PMID:Expression of p53 protein in benign epithelial hyperplasia, atypical ductal hyperplasia, non-invasive and invasive mammary carcinoma: an immunohistochemical study. 791 68

Salivary duct carcinoma is an infrequent highly aggressive salivary gland tumor that is histologically similar to ductal carcinoma of the breast. We studied 13 cases by immunohistochemistry for the presence of estrogen and progesterone receptors, cathepsin D, and c-erbB-2 protein to determine whether the similarity to breast carcinoma extended beyond the light microscope to the molecular level and, if so, whether these markers might have therapeutic or prognostic value. Twelve of 13 cases contained sufficient amounts of tumor tissue for evaluation. Of these 12 cases, one (8%) was positive for estrogen receptors, none was positive for progesterone receptors, five (42%) were positive for cathepsin D, and three (25%) were positive for c-erbB-2 protein. Expression of cathepsin D and c-erbB-2 protein does not appear to have prognostic significance in salivary duct carcinoma. The 8% incidence of immunopositivity for estrogen receptors and absence of progesterone receptors in salivary duct carcinoma is considerably less than that seen in breast cancer. Nevertheless, because the occurrence of systemic metastasis in salivary duct carcinoma is such an ominous development largely unresponsive to chemotherapy, antihormonal therapy, such as used in breast cancer, might be considered on a trial basis for those tumors that are estrogen receptor-positive when conventional therapeutic modalities fail.
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PMID:Salivary duct carcinoma. Part II. Immunohistochemical evaluation of 13 cases for estrogen and progesterone receptors, cathepsin D, and c-erbB-2 protein. 791 29

The clinicopathological and immunocytochemical features of nine cases of salivary duct carcinoma are described. This relatively rare tumour, which only recently has been widely recognized as a separate entity, is highly malignant and caused the death in eight of the patients. The tumour cells are arranged in cribriform and solid growth patterns, where the solid tumour nests frequently have comedo necrosis, and a fibrous, often sclerotic, stroma is present. The infiltrating desmoplasmic component and the diffuse invasive growth into adjacent adipose parotid tissue have similarities to ductal breast carcinoma. Immunocytochemical investigation of salivary duct carcinoma showed constant overexpression of c-erbB-2 as detected by membrane accentuation, and high proliferative activity as detected by nuclear positivity for MIB 1 (Ki-67). Changes in the expression of p53 and retinoblastoma gene product do not constitute a constant event in salivary duct carcinoma. A few of the tumours showed scattered cells with distinct nuclear positivity for both progesterone and oestrogen receptors. We emphasize that this highly malignant salivary gland tumour has a characteristic morphology, may not be as rare as previously considered, and that prompt and aggressive therapy is needed.
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PMID:Salivary duct carcinoma--a highly aggressive salivary gland tumour with overexpression of c-erbB-2. 793 25

Several investigators, the SEER data, and the ECOG/Intergroup study have shown that patients with small tumors (< 0.5 cm) have a recurrence rate of less than 2%, compared to 20-25% for large tumors (> or = 5 cm). Nuclear grade and tumor differentiation are established indicators; however, the interobserver lack of concordance has thwarted their use in clinical trials. The presence of peritumoral lymphatic and blood vessel invasion (PLBI) is associated with a relative risk of recurrence of 4.7. The predictive value of the presence of hormone receptors in tumors is associated with a favorable disease free and overall survival difference of 8-10%; however, this advantage is being eroded by the early appearance of other factors, such as the epidermal growth factor receptor (EGFR), proliferative capacity (S-phase), nuclear grade, and HER-2/neu oncogene. Concordance among the different methods of hormone-receptor assay (immunocytochemical, sucrose gradient, and dextran-coated charcoal) is essential to refine the true value of these factors. DNA flow cytometry measurements of ploidy (DNA content) and S-phase fraction are the most characterized of the prognostic factors. There are conflicting reports regarding the clinical significance of ploidy status, while measurements of S-phase fraction clearly indicate a robust association with disease free and overall survival. Our data continue to show that S-phase, but not ploidy, can predict time to recurrence significantly in untreated patients, even when data are stratified for tumor size. HER-2/neu oncogene is expressed in about 50% of ductal carcinoma in situ and 14% of invasive ductal carcinoma. The presence of this oncogene at high copy number may be a useful independent marker of poor prognosis and may be associated with drug resistance and correlated with tumor recurrence and shorter survival. EGFR could be measured in most breast tumors, and the level of its expression has inversely correlated with estrogen receptor protein expression. The value of EGFR as a predictor of prognosis remains controversial and is still being investigated. Cathepsin-D provides a provocative biologic rationale but is hindered by different and incongruent methods of analysis. The majority of large studies with more than 3-years' follow-up suggests that high cathepsin-D levels may be predictive of greater recurrence and lower survival. Angiogenesis has been implicated as a critical component of the metastatic process. Early studies show that tumor angiogenesis is an independent and highly significant prognostic indicator, and its presence may suggest the selection of "anti-angiogenic therapy."(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prognostic factors in early breast carcinoma. 800 12

Proliferating cell nuclear antigen (PCNA) appears in the cell nuclei during the late G1 to S phases of the cell cycle and is thought to be closely related to cellular proliferation. The authors have conducted an immunohistochemical study in order to investigate the tissue expression of PCNA and its clinical significance in breast cancer. Excluding cases with absolutely no positive cells on the section specimen, the mean value (%) for the PCNA labeling index (LI) was 30.4 in 187 cases of invasive ductal carcinoma. No correlations between PCNA LI and any clinicopathological factors such as tumor diameter and tumor stage were observed. Also, no significant correlation was observed with Ki-67 LI. A positive correlation was, however, observed with the tissue expression of c-erbB-2 protein. We divided 82 patients with stage II invasive ductal carcinoma into PCNA LI of < 10, PCNA LI of 10-50 and PCNA of > 50, and analyzed the specimens for any correlation with prognosis. The group with PCNA LI of > 50 had significantly poorer prognoses than the other groups. From the above, we concluded immunostaining for PCNA to be useful as a prognostic factor and as an indicator of the degree of malignancy in breast cancer.
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PMID:Proliferating cell nuclear antigen immunostaining in breast cancer and its relation to prognosis. 809 56

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

Growth factor-independent proliferation is an essential aspect of the transformation process. To study the influence of c-erbB-2 overexpression on the autonomous growth of human mammary cancer cells, we used a series of non-neoplastic and neoplastic human mammary epithelial cell lines isolated from a patient with intraductal and invasive ductal carcinoma of the breast. The non-neoplastic cell line, H16N-2, which expresses a normal level (single gene copy) of c-erbB-2, was used for comparison with the neoplastic cell lines. Both the metastatic tumor cell lines, 21MT-1 and 21 MT-2, showed equivalent amplification of the c-erbB-2 gene; however, 21MT-1 cells showed a higher level of c-erbB-2 overexpression. Therefore, the H16N-2, 21MT-2, and 21MT-1 cell series forms a distinct gradient of progressively increasing c-erbB-2 gene expression. Furthermore, the overexpression of c-erbB-2 in the 21MT cell lines was concordant with increases in the constitutive tyrosine kinase activity of p185erb-2 measured in the absence of exogenous growth factors in culture. Normal mammary epithelial cells require both insulin-like growth factor (IGF)-l (or supraphysiological concentrations of insulin) and epidermal growth factor (EGF) to proliferate under serum-free conditions in culture. By contrast, 21MT-2 cells showed a reduced requirement for IGF but still required EGF to proliferate. 21MT-1 cells did not require either insulin or EGF to proliferate. Therefore, the progressive increases in constitutive p185erbB-2, tyrosine kinase activity in the 21MT-2 and 21MT-1 cell lines was directly correlated with IGF independence and combined IGF and EGF independence under defined conditions in culture. Experiments using conditioned media and anti-IGF-1 receptor and anti-EGF receptor neutralizing antibodies showed that the growth-factor independence of the tumor cells did not involve detectable IGF- or EGF-like autocrine activity expressed by the 21MT cells. Furthermore, neu differentiation factor/heregulin, a ligand that indirectly activates p185erbB-2 by direct binding to erbB-3 receptors, potently stimulated the proliferation of the growth factor-dependent H16N-2 cells (which expressed c-erbB-2 and c-erbB-3 but not c-erbB-4) in the absence of both IGF and EGF. Thus, HRG-induced mitogenesis mimicked the autonomous growth seen in the 21MT cells that have the highest level of constitutive p185erbB-2 activation. These data support the hypothesis that the constitutive activation of p185erbB-2 in human mammary carcinoma cells causes growth-factor independence by directly activating multiple signal-transduction pathways that substitute for both IGF and EGF during proliferation.
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PMID:Insulin-like growth factor and epidermal growth factor independence in human mammary carcinoma cells with c-erbB-2 gene amplification and progressively elevated levels of tyrosine-phosphorylated p185erbB-2. 859 35

Immunohistochemically detected metallothionein expression [MT(+)] was shown to be related to aggressive behavior of the invasive ductal carcinoma of the breast. In this study, MT expression was examined immunohistochemically in 92 cases of invasive breast carcinoma and compared with immunohistochemically demonstrated estrogen receptor (ER), c-erbB-2, Ki-67 status and clinicopathological characteristics. Of the 92 cases examined, 27.1% (25 cases) were MT(+), and high percentages of the solid tubular subtype of invasive ductal carcinoma (47%), medullary carcinoma (80%), and carcinomas with spindle cell metaplasia (100%) were positive for MT. MT(+) carcinomas showed tendency to have highly atypical nuclei, and nuclear staining for Ki-67 antigen was found in a higher percentage of cases than in MT(-) carcinomas. An inverse relationship between MT(+) and ER immunoreactivity was observed. MT expression was not associated with age distribution, menopausal status, tumor size or lymph node metastasis. The overall survival rate in MT(+) cases was worse than in those negative for MT, but no significant association was found. MT(+) was not associated with poor prognosis in total, estrogen receptor-negative or node-negative tumors. These findings suggest that MT expression in breast cancer cells is related to cell-proliferative activity, and that dedifferentiation of carcinoma cells may play a role in induction of MT expression.
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PMID:Immunohistochemical expression of metallothionein in invasive breast cancer in relation to proliferative activity, histology and prognosis. 860 36

Histological examination of invasive ductal carcinoma of the breast often demonstrates the presence of an extensive central fibrotic focus (FF). The clinicopathological significance of the FF, or scar, in primary invasive ductal carcinoma is still ambiguous. One hundred and fifty-three cases of invasive ductal carcinoma (IDC) were classified into two groups, those with and those without FF. The differences in frequency of immunohistochemically detected overexpression of c-erbB-2 protein and nuclear accumulation of p53 protein, and the labeling index of proliferating cell nuclear antigen (PCNA), as well as histopathological parameters were compared between these two groups. IDCs smaller than 50 mm with FF showed a higher frequency of high-grade tumors, a higher frequency of lymph node metastasis, and a significantly higher frequency of c-erbB-2 protein overexpression than those without FF. In tumors of 20 mm or less, the incidence of nuclear accumulation of p53 protein was significantly higher in tumors with than those without FF. Tumors with FF showed a significantly higher PCNA labeling index than those without FF, regardless of tumor size. The present results indicate that the presence of FF is an important clinicopathological parameter associated with a higher degree of malignancy in IDCs, especially those smaller than 50 mm. Therefore, dividing IDCs into those with and those without FF appears to be meaningful clinicopathologically.
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PMID:Fibrotic focus in invasive ductal carcinoma: an indicator of high tumor aggressiveness. 864 70


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