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)

An immunohistochemical study of c-erbB-2 expression was carried out on in situ (non-invasive) breast carcinoma, using antibody 21N, raised to the intracytoplasmic domain of the c-erbB-2 oncogene product. Strong membrane staining was observed in 44 out of 74 (59 per cent) cases of ductal carcinoma in situ (DCIS), but none of 48 lobular carcinoma in situ (LCIS) lesions. A detailed comparative morphological evaluation using several different parameters, including histological subtypes, was performed within the DCIS group. The results showed that there was a significant correlation between c-erbB-2 expression and the presence of large cell size, periductal lymphoid cell infiltration, marked nuclear pleomorphism, multinucleation, and a high mitotic rate. Of these, cell size appears to be the most important predictor of c-erbB-2 status, followed by the presence of periductal lymphoid cell infiltration. These results indicate, firstly, that LCIS and DCIS are biologically (as well as histologically) different and, secondly, that a subgroup of DCIS, which is associated with c-erbB-2 over-expression, exists and appears to have distinct histological features. The subgroup of DCIS cases which over-express c-erbB-2 may be a biologically definable category with prognostic importance. These results may therefore have relevance to breast screening programmes, but a larger study incorporating clinical data would be necessary to correlate these findings with clinical outcome.
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PMID:Immunohistochemical distribution of c-erbB-2 in in situ breast carcinoma--a detailed morphological analysis. 197 59

Cases of ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH) of the breast were examined for expression of the protein product of the c-erbB-2 (neu, HER-2) oncogene using two different polyclonal antibodies via an avidin-biotin immunoperoxidase method on formalin- or Bouin'-fixed, paraffin-embedded tissue. Fifty-five percent (18/33) of DCIS and 10% (2/21) of ADH were positive. Significant c-erbB-2 expression in DCIS was generally divided on histologic grounds: ten of ten comedocarcinomas showed strong membrane staining, while only one of 14 small cell DCIS cases (micropapillary or cribiform patterns) showed immunostaining (which was weak and basilar in this single case). DCIS cases of mixed histology were strongly positive in areas of comedocarcinoma. In two of three cases of associated Paget's disease strong membrane staining was seen. The two c-erbB-2-positive ADH cases showed weak basilar staining akin to the small cell DCIS cases. Five cases of lobular neoplasia (atypical lobular hyperplasia or lobular carcinoma in situ) associated with DCIS or ADH were negative for c-erbB-2 expression. We conclude that comedocarcinoma in situ and Paget's disease frequently express the c-erbB-2 protein and are both histologically and biochemically distinct from ADH and small cell patterns of DCIS. We advocate precise subclassification of DCIS on histopathologic reports, particularly in view of reports that overexpression of the c-erbB-2 oncogene in infiltrating breast carcinomas may be associated with a poor prognosis.
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PMID:Immunohistochemical evaluation of c-erbB-2 oncogene expression in ductal carcinoma in situ and atypical ductal hyperplasia of the breast. 217 Sep 71

In 74 in situ breast cancers an immunohistochemical study for estrogen (ER) and progesterone (PR) receptors, proliferation index (PI), and c-erbB-2, p53, and bcl-2 overexpression was performed. Cases were categorized as ductal carcinoma in situ (DCIS) comedo: 24.3% of cases; DCIS non comedo: 27% of cases; DCIS cribriform: 5.4% of cases; lobular carcinoma in situ (LCIS): 16.3% of cases; mixed carcinoma in situ: 27% of cases. Quantitation of immunohistochemical results was obtained with an image analysis computerized system (CAS 200). The cutoff values used were: 10% of positive area for ER, PR, NEU, and bcl-2; 5% of positive area for p53; 13% of PI for proliferative activity. DCIS cribriform and LCIS displayed a higher positivity for ER (92.6 and 93.8% of cases); DCIS cribriform and DCIS non comedo a higher for PR (89 and 75.3%); DCIS comedo presented the highest values for PI (65.4%), NEU (72.8%), and p53 expression (37.3%). All DCIS cribriform and DCIS non comedo and 99.6% of LCIS expressed bcl-2. The results underscore the importance of biological characterization of breast carcinoma in situ with the aim to define lesions natural history.
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PMID:Biological profile of in situ breast cancer investigated by immunohistochemical technique. 967 74

Axillary lymph node status is an important prognostic feature for patients with breast cancer, but the therapeutic value of axillary lymphadenectomy is controversial. It would be useful to be able to predict the status of axillary lymph nodes before lymphadenectomy from prognostic features evaluated in a previous breast biopsy. This prediction would be useful to optimize the treatment of patients with breast cancer who are unlikely to have nodal metastases. We studied 279 patients with invasive breast carcinoma treated with modified radical mastectomy or with lumpectomy combined with axillary lymph node dissection. Prognostic factors evaluated were age, histologic type of invasive tumor, presence of associated ductal and/or lobular carcinoma in situ, lesion size, histologic and nuclear grades, DNA index, presence of multiploidy by flow cytometric analysis, and immunocytochemical expression of estrogen and progesterone receptors, proliferating nuclear cell antigen, and HER-2/neu oncogene. Several probabilistic neural networks (NNs) with genetic algorithms were developed using prognostic features as input neurons and lymph node status (positive or negative) as output neurons. The data were also studied with multiple regression and logistic regression analysis. The best NN model trained with 224 cases using 19 input neurons. It classified correctly 49 (89.0%) of 55 unknown cases (specificity, 97.2%; sensitivity, 80.0%; positive predictive value, 93.8%; negative predictive value, 87.5%). Several statistically significant models could be fitted with both multiple regression and logistic regression. The logistic regression model fitted with 240 cases using 6 independent variables estimated correctly 26 (66%) of 39 holdout cases. NNs and logistic regression models offer potentially useful tools to estimate the status of axillary lymph nodes of breast cancer patients before axillary lymphadenectomy. Future prospective studies with larger groups of patients and perhaps better prognostic markers are needed before these predictive multivariate models become ready for clinical use.
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PMID:Reasoning with uncertainty in pathology: artificial neural networks and logistic regression as tools for prediction of lymph node status in breast cancer patients. 1034 89

In a consecutive and unselected series of 178 cases of carcinoma in situ of the breast (CIS), comprising both ductal (DCIS) and lobular type (LCIS), and a series of 48 cases of invasive carcinoma (IC) with predominance of DCIS, the association between histopathology, immunohistochemical markers (ER, PgR, MIB-1, c-erbB-2, and p53), and DNA ploidy was investigated, in order to discriminate biologically different groups. In DCIS, significant correlation was shown between large nuclear size and comedonecrosis, both of which showed also strong association to DNA aneuploidy, high proliferation activity, low steroid receptor content, and overexpression of c-erbB-2 and p53 factors that may indicate an aggressive behavior. Small nuclear CIS, whether LCIS or DCIS, on the contrary, were DNA diploid with low proliferation, and no cases showed overexpression of c-erbB-2 and p53. Heterogeneity with respect to the investigated parameters was also a frequent finding that may reflect a development complexity. In IC, comparison of the DCIS and the invasive component showed similar patterns. No significant differences were shown between DCIS without and with invasion. This may indicate that none of the investigated parameters on its own are essential for the event of invasion.
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PMID:Carcinoma in situ of the breast: correlation of histopathology to immunohistochemical markers and DNA ploidy. 1093 Jan 9

We reviewed 10 cases of pleomorphic lobular (ductal lobular) carcinoma in situ (PL/DLCIS) of the breast and compared them with 14 cases of pleomorphic lobular carcinoma in situ (PLCIS) found in association with invasive pleomorphic lobular carcinoma. The histologic features; immunohistochemical staining for estrogen receptors (ERs), p53, Ki67, E-cadherin, and gross cystic disease fluid protein-15 (GCDFP-15); and results of fluorescence in situ hybridization for HER-2/neu gene amplification were evaluated in all 24 cases. Histologically, PL/DLCIS cells were similar to those of PLCIS with invasion in that they were discohesive and medium to large in size with moderate to marked nuclear pleomorphism, small to prominent nucleoli, and moderate to abundant eosinophilic or vacuolated cytoplasm. In both groups, central necrosis was present in a small number of cases, and classic LCIS coexisted with the in situ lesion in less than half of the cases; in situ carcinomas were positive for ERs in 23 (100%) of 23 cases, p53 in 6 (25%) of 24 cases, and GCDFP-15 in 14 (74%) of 19 cases. The percentage of Ki67-positive tumor nuclei indicated moderate to high (more than 20%) proliferative activity in 8 (47%) of 17 cases. Immunostaining for E-cadherin was negative in all 24 cases. HER-2/neu gene amplification was observed in 1 (4%) of 23 cases. In cases with associated invasion, PLCIS had cytologic features and immunostaining patterns similar to those of the invasive pleomorphic component. Seven of the 10 patients who had PL/DLCIS without invasion underwent lumpectomy or simple mastectomy. Six of these patients had no evidence of disease in follow-up periods ranging from 4 to 32 months; the seventh patient developed recurrent disease 12 months after undergoing lumpectomy. We conclude that the cytologic features and biomarker expression profile of PL/DLCIS are similar to those of PLCIS with invasion but somewhat different from those of classic LCIS and ductal carcinoma in situ. Long-term follow-up studies are needed to further define the natural history of PL/DLCIS and its optimal management.
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PMID:Clinical, histopathologic, and biologic features of pleomorphic lobular (ductal-lobular) carcinoma in situ of the breast: a report of 24 cases. 1237 50

Carcinoma in situ of the breast (CIS) comprise a heterogenous group of lesions, covering a wide spectrum of clinical conditions and histopathological changes. With respect to biological behavior, CIS range from biologically aggressive lesions with a substantial risk of progression into invasive carcinoma (IC), to lesions with a very low malignant potential. Two main types of CIS are described--ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). Previous studies of CIS indicate that approximately a third will subsequently develop IC. Autopsy studies indicate that CIS is frequently occurring and it was estimated that about 20% of all women will develop CIS during lifetime. Only a minor fraction is ever diagnosed, although the incidence of DCIS is increasing, especially related to mammography screening. The lack of knowledge about the biological significance of the histopathological subtypes was the background of the present study. In 1982, a nationwide, prospective study of CIS (protocol DBCG 82-IS) was initiated by the Danish Breast Cancer Cooperative Group (DBCG). From this protocol, the group of patients treated with breast conservation surgery (BCS) constituted the material for clinico-histological investigation. A total of 275 women were included in the period 1982-89. Follow-up studies showed that recurrence rate was significantly related to nuclear size of the primary lesion. Since nuclear changes might be related to DNA content and, furthermore, many invasive breast carcinomas were shown to be DNA aneuploid, flow cytometric (FCM) DNA ploidy analysis was performed in a series of DCIS lesions. More than 80% of these lesions were DNA aneuploid, with a distribution similar to that found in invasive carcinomas. This finding raised the hypothesis that the DNA pattern of an invasive carcinoma was already established at the preinvasive stage of DCIS. Therefore, FCM DNA analysis was performed on a series of ICs with predominance of DCIS. Partial or complete concordance in DNA ploidy between DCIS and IC within the individual case was found in most cases, except for the additional presence in the IC component of DNA hyperdiploid clones that might possibly be of importance for the process of invasion. In order to further characterize CIS lesions and, possibly, to discriminate biologically different groups, immunohistochemical markers were investigated in a consecutive series of CIS and IC with predominance of DCIS. The results were correlated to the histopathological and DNA ploidy findings. In DCIS, significant correlation was shown between large nuclear size and comedonecrosis, both of which showed also strong association to DNA aneuploidy, high proliferation activity, low steroid receptor content, and overexpression of c-erbB-2 and p53--factors that may indicate an aggressive behavior. Small nuclear CIS, whether LCIS or DCIS, on the contrary, were DNA diploid with low proliferation, and no cases showed overexpression of c-erbB-2 and p53. In IC, comparison of the DCIS and the invasive component showed similar patterns. No significant differences, in neither morphology, immunohistochemistry, nor DNA ploidy, were shown between DCIS without and with invasion. These findings may indicate that none of the parameters in question may on its own be essential for the decisive event of invasive growth.
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PMID:Carcinoma in situ of the female breast. A clinico-pathological, immunohistological, and DNA ploidy study. 1287 68

PC-cell-derived growth factor (PCDGF, progranulin) is a novel autocrine growth factor that is overexpressed in human breast cancer cell lines. We have examined immunohistochemical PCDGF expression in 206 paraffin-embedded human breast lesions and investigated its association with clinicopathological variables. PCDGF staining was observed in breast carcinoma, whereas it was almost always negative in benign breast epithelium. PCDGF expression was more common in invasive ductal carcinoma (80% cases positive) than in invasive lobular carcinoma (53% positive). PCDGF staining was almost never observed in lobular carcinoma in situ. Ductal carcinoma in situ expressed PCDGF in 66% of the cases, and this expression correlated strongly with nuclear grade. Similar correlation was observed between PCDGF expression and histologic grade of invasive ductal carcinoma. Average Ki-67 index of PCDGF-negative/weakly positive invasive carcinomas (30.3) was significantly lower than that of strongly PCDGF-positive tumors (48.8, P=0.01). A larger percentage of tumors that expressed PCDGF with a staining intensity of 2+ or 3+ were p53 positive (44%) than were PCDGF-negative tumors (25%), P=0.02. PCDGF expression was independent of c-erbB-2 overexpression and of ER and PR status. Our study provides the first evidence of high incidence of PCDGF expression in human breast cancer in which it correlates with clinicopathological variables such as tumor grade, proliferation index, and p53 expression. These characteristics, as well as the virtual absence of expression in benign breast tissue, suggest an important role of PCDGF in breast cancer pathogenesis and make it a potential novel target for the treatment of breast cancer.
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PMID:Expression of PC-cell-derived growth factor in benign and malignant human breast epithelium. 1465 16

The predisposition of patients with lobular carcinoma in situ (LCIS) to develop invasive breast cancer (IBC) is well known. However, relatively little is known about the biologic characteristics, which may be involved in the development and progression of LCIS. This study evaluated 59 cases of LCIS (29 pure, 30 with synchronous IBC) for five biomarkers known to be important in IBC (ER, PgR, c-erbB-2, p53 and Ki-67 proliferation rate) by immunohistochemistry. A comprehensive analysis of loss-of-heterozygosity (LOH) was performed in 12 cases (10 pure, 2 with synchronous IBC) at 15 genetic loci on 9 chromosomes. LCIS demonstrated a low grade/favorable biophenotype that was not significantly different in cases with and without synchronous IBC (ER 98%, PgR 84%, c-erbB-24%, p53 19% and proliferation rate 2%). LOH was present in 80% of pure LCIS and the highest rates of LOH were at loci on 9p (30%), 16q (63%), 17p (33%) and 17q (50%). The clustering of LOH at these four foci suggests that inactivated tumor suppressor genes in these regions may be particularly important. LOH was present in both cases of LCIS with synchronous IBC and the LOH phenotype was shared by LCIS and IBC. Our findings suggest that five known prognostic factors in IBC do not have prognostic utility in LCIS. Multiple genetic mechanisms may be involved in the development of LCIS.
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PMID:Biomarker profile and genetic abnormalities in lobular carcinoma in situ. 1583 Jan 38