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 overexpression of the c-erbB-2 oncoprotein has been demonstrated in the breast cancer and has been associated with a poor prognosis. Our study involved 23 cases of mammary Paget's disease which was found to be associated with the intraductal carcinomas in 13 cases, the intraductal carcinomas supposed micro-invasive in 2 cases, the infiltrating ductal carcinomas with predominant intraductal component in 6 cases and the infiltrating ductal carcinomas in 2 cases. The presence of c-erbB-2 oncoprotein has been determined immunohistochemically with 3 different antibodies: rabbit anti-human c-erbB-2 oncoprotein A485 (Dako), c-erbB-2 oncoprotein (internal domain) mouse monoclonal antibody NCL-CB11 (Novocastra), and c-erbB-2 oncoprotein (external domain) mouse monoclonal antibody NCL-CBE1 (Novocastra). An overexpression of the c-erbB-2 oncoprotein has been observed in 21 of the 23 studied cases. We noted an intense membrane staining in the intraepidermal or intraglandular tumour cells of mammary Paget's disease. Any staining has been observed in 2 cases with glandular component of pure intraductal type. These results are identical whatever the antibody used. In a previous study concerning mammary Paget's disease, it has been noted a correlation between this overexpression and presence of large malignant cells. We also have found this notion in mammary Paget's disease where the c-erbB-2 positive neoplastic cells in the different tumour components were large with prominent cytoplasm. The obtained results argue strongly for adenocarcinomatous origin for mammary Paget's disease and exhibit that the overexpression of c-erbB-2 oncoprotein was not constantly in correlation with a poor prognosis.
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PMID:[Expression of the c-erbB-2 oncoprotein in mammary Paget's disease. Immunohistochemical study by using 3 antibodies]. 857 Feb 62

The paraffin sections from 20 nipples with Paget's disease (10 central intraductal and 10 invasive ductal carcinomas) were analyzed for human papilloma virus (HPV) DNA of the low- and intermediate/high-risk groups. Polymerase chain reaction (PCR) and dot (slot) blot hybridization were used for the detection of HPV DNA types 6/11/16/18/31/33/35. In addition, we examined the c-erbB-2 oncogene expression in the specimens to differentiate benign cells in the surface epithelium of the nipple and areola from Paget cells. We found that the oncogene expression of the c-erbB-2 displayed a strong signal in the Paget cells. Using PCR and dot (slot) blot hybridization, we could not detect the HPV DNAs that are specific for the low- and intermediate/high risk-groups in the 20 cases of Paget's disease. Our results showed for the first time that this type of virus did not contribute to the pathogenesis of Paget's disease.
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PMID:Human papilloma virus DNA: a factor in the pathogenesis of mammary Paget's disease? 893 76

A comparative immunohistochemical study was performed on Paget's disease of the nipple (PDN), extramammary Paget's disease (EMPD) and cutaneous superficial spreading melanoma (SSM) using antibodies to S100, NK1-C3 and HMB45, cytokeratin (CAM 5.2) and c-erb B2 oncoprotein (21N). Conventional histochemical stains for intracytoplasmic mucin and melanin were also done. Of the 20 cases of PDN, positivity was seen in 12 with S100, 16 with NK1-C3, none with HMB45, 20 with CAM 5.2 and 19 with 21N. All 5 cases of EMPD were CAM 5.2 positive and HMB45, S100 and 21N negative. Three EMPD were NK1-C3 positive. All 10 cases of SSM were S100, NK1-C3 and HMB45 positive and all were CAM5.2 and 21N negative. Mucin was demonstrable in 11 cases of PDN and all of EMPD but none of SSM. Melanin was seen in 2 PDN, 3 EMPD and all SSM cases. Identification of mucin and melanin, therefore, proved an unreliable means of distinguishing these diseases. Immunohistochemistry for cytokeratin and HMB45 appear to be the most specific markers in differentiating Paget's disease and SSM. Antibodies to c-erb B2 may also be valuable in this situation.
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PMID:A comparative immunohistochemical study of mammary and extramammary Paget's disease and superficial spreading melanoma, with particular emphasis on melanocytic markers. 898 82

Extramammary Paget's disease is a particular form of skin cancer of unknown histogenesis. To look for the genetic defects underlying the pathogenesis of this tumour, we have examined loss of heterozygosity (LOH), p53 and human papillomavirus (HPV) status, and the expression of c-erbB-2 and bcl-2 proteins in 14 cases. Unexpectedly, no LOH was detected at several loci commonly lost in other human cancers (namely 3p, 9p, 9q, 13q, 16q, 17p, and 17q) in 12 tumours examined. Altered p53 protein expression was entirely or mostly negative in all 14 cases. Direct sequencing of exons 5-8 of the p53 gene in eight cases revealed no mutation. Polymerase chain reaction amplification of the L1 gene of human papillomavirus (HPV) did not detect the virus that could inactivate p53 and retinoblastoma tumour-suppressor gene products. As expected, c-erbB-2 proto-oncogene protein was overexpressed in six cases. The expression of bcl-2 was negative in all cases. The results presented in this study suggest that molecular events underlying extramammary Paget's disease differ from those of other common epithelial malignancies and that tumour-suppressor genes located in chromosome regions not examined in this study may be important.
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PMID:Tumour cells of extramammary Paget's disease do not show either p53 mutation or allelic loss at several selected loci implicated in other cancers. 932 50

Our previous study in extramammary Paget's disease showed neither p53 mutations nor allelic loss at selected loci implicated in other cancers, suggesting a pathogenesis of this skin cancer different from other common epithelial malignancies. To examine further the genetic defects in extramammary Paget's disease, we carried out molecular genetic analyses in 31 tumor samples obtained from 27 cases of extramammary Paget's disease without underlying malignancies. Immunohistochemistry using CB-11 monoclonal antibody revealed either membrane or cytoplasmic erbB-2 oncoprotein overexpression in none of the 13 primary in situ tumors, but in one recurrent in situ tumor, 10 of 13 invasive primary tumors and two of four lymph node metastases. Sensitive dual color fluorescence in situ hybridization analysis using probes for erbB-2 gene locus and chromosome 17 pericentromere, however, revealed different erbB-2 gene status in the erbB-2 overexpressing tumors. One recurrent in situ tumor and one lymph node metastasis showed definite gene amplification characterized by multiple scattered signals or a few large clustered erbB-2 signals, whereas four tumors with predominantly cytoplasmic erbB-2 overexpression were thought to have low-grade gene amplification. The remaining six tumors overexpressing erbB-2 showed no increase of erbB-2 copy numbers. No evidence of abnormal activation of the beta-catenin gene, a critical mediator of Wnt signaling pathway, in any tumor by immunohistochemical staining and by direct sequencing and reverse transcription-polymerase chain reaction analysis was found. Frequent overexpression of erbB-2 by either gene amplification or possible transcriptional activation in invasive primary tumors and metastases suggests an important part for this oncogene in the progression of extramammary Paget's disease.
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PMID:erbB-2 overexpression but no activation of beta-Catenin gene in extramammary Paget's disease. 1046 13

The HER-2/neu proto-oncogene amplification or oncoprotein overexpression is an important prognostic factor and a predictive factor for resistance to endocrine therapy and adjuvant chemotherapy in breast cancers. Moreover, it is an entry criterion in the assessment of patients for whom Herceptin (Trastuzumab) treatment is considered. The overexpression rate of HER-2/neu oncoprotein has been identified in 10% to 40% of human breast cancers. In Taiwan, a higher grade of pathobiologic characteristics of familial breast cancer was also noted than that found in the non-familial group. It is worthwhile to evaluate whether the overexpression is more frequent in familial breast cancers. Fifty-six familial and 111 non-familial breast cancers were studied between 1990 and 1999 to assess both the overexpression of HER-2/neu oncoprotein immunohistochemically and the correlation with the histological type, grade and stage of breast carcinoma. The overexpression rate is higher in the familial breast cancer group (50.0%) when compared with non-familial breast cancer group (36.9%), which did not prove to be statistically significant (P = 0.1068). However, when the infiltrating ductal carcinomas of both groups are compared, it is statistically significant (52.3% vs. 33.7%, P = 0.0429). Overexpression correlated with node status and histological grade of infiltrating ductal carcinomas in non-familial and overall breast cancers. It also correlated with nuclear pleomorphism and mitotic counts, but not tubule formation or tumor size. All 3 cases of Paget's disease revealed overexpression, whereas all 12 cases of mucinous and one case of metaplastic carcinoma and one case of medullary carcinoma were negative. The overexpression rate was higher both in familial and non-familial intraductal carcinomas (57.1% vs. 73.3%, P = 0.4716). No statistical difference was identified between the 2 subsets. A case of infiltrating ductal carcinoma combined with intraductal carcinoma revealed heterogeneous staining in the component of ductal carcinoma in situ, while the invasive component did not. This suggests that overexpression decreases within individual tumors as they evolve from in situ to invasive lesioins. The HER-2/neu may imply a different role in intraductal carcinoma, Paget's disease and invasive duct carcinoma. Although the overexpression rate of HER-2/neu oncoprotein of familial breast cancer was not significantly higher than that of the non-familial group, it is appropriate to evaluate the rate of HER-2/neu overexpression according to the histological type of breast cancers from familial breast cancer and non-familial breast cancer. The prognoses will be needed for future evaluation.
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PMID:Expression of HER-2/NEU oncoprotein in familial and non-familial breast cancer. 1141 60

We describe a very rare association between intraepithelial, extramammary Paget's disease and human papillomavirus- (HPV) negative, keratinized type of VIN III observed in two elderly women. In both cases, morphological and immunohistochemical investigation showed two heterogeneous but intimately admixed neoplastic populations of vulvar epithelium. Atypical keratinocytes stained markedly and diffusely positive for high molecular weight cytokeratins, and moderately for p53 protein and c-erbB-2 immunostainings. Paget cells were diffusely positive for CEA, EMA, and low molecular weight cytokeratins, moderately and focally for c-erbB-2 and (in one case) for S-100. Morphological and immunohistochemical phenotypic differences between Paget cells and atypical keratinocytes suggest a simultaneous and incidental association of two distinct neoplastic disorders more than a mixed carcinoma in situ of vulvar epithelium.
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PMID:Simultaneous vulvar intraepithelial neoplasia and Paget's disease: report of two cases. 1143 29

To investigate at the population level the impact of BRCA1/BRCA2 gene alterations in male breast cancer, we analyzed a population-based series of 25 male breast cancer cases from Florence, Central Italy. We combined mutational screening with the study of germ-line allele transcript levels and of tumor-associated losses of heterozygosity. Screening by protein truncation test and single-strand conformational polymorphism assay, followed by sequencing, revealed 4 pathogenetic mutations (4 of 25 = 16%; 95% confidence interval, 5-37%), 1 in BRCA1 and 3 in BRCA2, including mutations recurring in Central Italy (BRCA1 3345delAG and BRCA2 6696delTC). The a priori probability of carrying a mutation, estimated using BRCAPRO software, showed a good agreement between expected and observed mutations (14% versus 16%). A 7-fold association between germ-line mutations and family history of breast-ovarian cancer emerged. To investigate associations between BRCA1/BRCA2 status and clinicopathological characteristics, we analyzed the histopathological and immunophenotypic parameters of the tumors. A significant association emerged between mutation carrier status and high histological grade (P = 0.02). Furthermore, one BRCA2 carrier was affected with Paget's disease, an extremely rare male breast cancer histotype. Overall, BRCA1/2 mutations were observed to be strongly associated with positive c-erbB-2 immunostaining (P = 0.004). To evaluate germ-line allele expression, we used primer extension assays targeting frequent BRCA1 and BRCA2 polymorphisms. A BRCA2 allele transcript imbalance was found in one of four heterozygotes tested, all of them negative for germ-line mutations. BRCA1 transcript imbalances were not detected in nine heterozygotes analyzed. Losses of heterozygosity at one or more of nine loci in the BRCA2 region were found in 8 of 22 tumors tested. Interestingly, a case that was negative for BRCA1/BRCA2 germ-line mutations and that had a priori mutation probability <10% showed loss of heterozygosity at all three of the intragenic BRCA2 markers analyzed, which could be related to a somatic involvement of BRCA2. No losses of heterozygosity were detected at BRCA1. In conclusion, constitutional BRCA1/BRCA2 mutations accounted for 16% of the male breast cancer cases in this area of Central Italy. The detection of a BRCA2 germ-line transcript imbalance and of a somatic loss of BRCA2 among the cases that resulted negative for germ-line mutations suggests a role of this gene more relevant than indicated by conventional mutational analysis. A distinct pattern of characteristics indicative of aggressive behavior, including high-grade and c-erbB-2 expression, was evident in tumors from germ-line BRCA2 mutation carriers. This suggests that phenotypic characteristics may contribute to the identification of hereditary BRCA2-related male breast cancers and that these tumors might share a unique molecular pathway of cancer progression.
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PMID:BRCA1 and BRCA2 mutation status and tumor characteristics in male breast cancer: a population-based study in Italy. 1254 86

Clinically, it is difficult to differentiate between nipple duct adenomas (NDAs) and Paget's disease of the nipple. These lesions share similar morphological and histological characteristics. Clear cell types present in NDA, epidermal clear cells (ECC) and Toker cells (TC), share immunoreactive similarities to Paget cells which can lead to confusion in classification. The aim of this study was to obtain information on the characteristics and histogenesis of ECC and TC, to distinguish these cells from Paget cells. Ten nipple epidermal with NDA were compared to 25 histologically normal nipples. Samples were analyzed for cytokeratins (CKs) 7, 8 and 18, carcinoembryonic antigen (CEA), c-erbB-2/HER2 expression and human papillomavirus (HPV-) DNA. In 13 out of 25 normal nipples the staining sequence demonstrated that ECC and TC cell types are immunoreactive with CKs 7, 8 and 18 in the basal region of the epidermis. In contrast, aggregated CKs 7, 8 and 18-immunoreactive ECC and TC were identified in the epidermal of 8 of the 10 NDA cases. In 2 cases, TC were continuous with the underlying NDA, suggesting that TC might be of ductal origin and migrate through the galactophorous ostia. In NDAs and 25 histologically normal nipples, ECC and TC were negative for CEA, c-erbB-2/HER2 and HPV-DNA. ECC and TC, normally present in the nipple epidermis, may proliferate and form aggregates in the presence of an underlying NDA. These cells show immunoreactivity for CKs 7, 8 and 18 but are negative for c-erbB-2/HER2, CEA and HPV-DNA and should not lead to the mistaken diagnosis of Paget's disease.
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PMID:Characteristics of clear cells and Toker cells in the epidermis of underlying nipple duct adenoma. 1255 78

The histogenesis as well as the biological and molecular differences in mammary Paget's disease (MPD) and extramammary Paget's disease (EPD) are not well understood. HER-2/neu oncogene overexpression is associated with poor prognosis in breast cancer patients. It is also believed that the spread of Paget's cells through the epidermis is induced by a motility factor that acts via the HER-2/neu receptor. However, previous studies on HER-2/neu expression in MPD and EPD have given conflicting results. Recent studies have suggested that vimentin expression in breast cancer confers a more aggressive phenotype with a possible role in tumor invasion and metastasis. We examined 58 cases of MPD and EPD for HER-2/neu overexpression and vimentin status to study the role of these markers in the production of the Paget's phenotype. Thirty-five of the 38 cases (92.1%) of MPD were associated with an underlying carcinoma, while none of the cases of EPD were associated with an underlying malignancy. Thirty-six of the 38 cases of MPD (94.7%) overexpressed the HER-2/neu oncoprotein and 17 cases (44.7%) showed vimentin expression. In contrast, only 1 of the 20 cases of EPD (5%) showed positivity for HER-2/neu oncoprotein and all were negative for vimentin. Our results indicate that the cell motility enhancing effect of HER-2/neu oncoprotein and possibly vimentin plays a significant role in the pathogenesis of MPD which appears to be a pagetoid spread of an underlying ductal malignancy (secondary), while EPD is an in situ malignant transformation of a totipotential epidermal cell or glandular epithelium.
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PMID:The role of HER-2/neu oncogene and vimentin filaments in the production of the Paget's phenotype. 1461 43


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