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 occurrence of epithelial membrane antigen (EMA), low molecular weight cytokeratin (CK) and erbB-2 oncoprotein was investigated in twenty-eight cases of Paget's disease of the nipple (PD) to determine their diagnostic usefulness. The ABC technique with monoclonal antibodies was used on formalin-fixed, paraffin-embedded tissue. The Paget's cells showed positive immunoreactivity for all three antigens investigated in a high percentage of PD. Immunoreactivity for CK and erbB-2 oncoprotein was restricted to the Paget's cells, whereas EMA in some cases also stained the adjacent keratinocytes. Since CK and/or erbB-2 oncoprotein occurred in 93% of the cases, we conclude that demonstration of both antigens is useful in the diagnosis of PD. ErbB-2 oncoprotein was also found to be expressed in a high percentage of the underlying intraductal and invasive carcinomas.
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PMID:Expression of cytokeratin and erbB-2 oncoprotein in Paget's disease of the nipple. An immunohistochemical study. 128 21

Immunohistochemical c-erbB-2 proto-oncogene expression and nuclear DNA distribution patterns were assessed in 119 formalin-fixed paraffin-embedded surgical specimens of human mammary carcinomas in situ (CIS). The series consisted of 107 ductal carcinomas in situ (DCIS), 9 lobular carcinomas in situ, and 3 cases of Paget's disease of the nipple. Nuclear DNA distribution patterns were assessed by image cytometric analysis of histopathologically identified cell nuclei. Fifty-one of 107 (48%) DCIS were immunoreactive for c-erbB-2, whereas specific cell membrane staining was absent in lobular carcinomas in situ. The neoplastic cell nuclei of 46 CIS (39%) were of DNA diploid type, and 73 CIS (61%) contained aneuploid nuclear DNA. Among various histopathologic subtypes of DCIS, significant differences in c-erbB-2 immunoreactivity and nuclear ploidy were observed. DCIS of the comedo type most often were c-erbB-2 positive and exhibited aneuploid nuclear DNA histograms. DCIS of micropapillary type was the second most frequently reactive c-erbB-2 expression, and aneuploidy were less common in solid, cribriform, and papillary DCIS. The results of the current study indicate that immunohistochemical expression of the c-erbB-2 proto-oncogene product is closely related to the histopathologic subtype and the nuclear DNA content of mammary CIS. Examples of CIS that are c-erbB-2 immunoreactive and DNA aneuploid seem to have a significantly higher risk for the subsequent development of infiltrating mammary carcinoma.
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PMID:Immunohistochemical c-erbB-2 protooncogene expression and nuclear DNA content in human mammary carcinoma in situ. 137 18

Tumours from 45 patients with Paget's disease of the nipple have been stained with antibody 21N which was raised against a peptide from the C-terminus of the predicted c-erbB-2 protein. Positive staining was observed in 41 cases (91%). In 42 cases the underlying mammary carcinoma was also available for study. In all but two cases staining was similar in the Paget's cells and the underlying carcinoma whether the latter was purely in situ ductal (35%) or in situ associated with infiltrating carcinoma (65%); the malignant cells in both components were large and pleomorphic and the in situ ductal carcinoma was of the comedo type. In the two exceptions the underlying carcinoma showed different histological features. The significance of the high levels of c-erbB-2 protein in this pattern of mammary carcinoma is considered.
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PMID:An immunohistochemical study of the presence of c-erbB-2 protein in Paget's disease of the nipple. 257 5

The c-erbB-2 oncogene has been extensively studied in mammary carcinomas since Slamon and colleagues demonstrated the association between amplification and poor prognosis in 1987. Further work found that amplification was accompanied by overexpression of the protein; however, this relationship is not perfect. Recently, Hollywood and Hurst have shown increased transcription in some cell lines containing a single copy of the gene, causing mRNA accumulation in overexpressing cells. Protein expression appears to be a good indicator of various abnormalities in the c-erbB-2 gene. Fortunately, c-erbB-2 protein, unlike epidermal growth factor (EGF) receptor, survives most fixation procedures used in routine histopathology laboratories. This has enabled immunohistochemical studies to be carried out on archival material. A higher incidence of c-erbB-2 positivity occurs in ductal carcinoma in situ (DCIS) than in infiltrating carcinomas. In DCIS there is a very close association between protein expression and high grade (comedo type). This explains the very high incidence of c-erbB-2 positivity in Paget's disease of the nipple which is nearly always associated with high grade DCIS. A lower proportion of high grade infiltrating carcinomas express the protein, highlighting the difference in incidence of positivity in the two types of ductal lesion. As well as having a potential role in the biological classification of mammary carcinomas, c-erbB-2 expression has been used to predict response to treatment. There have been reports that tumors expressing c-erbB-2 fail to respond to either chemotherapy or endocrine therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:c-erbB-2 amplification in mammary carcinoma. 791 60

Paget's disease of the nipple is a rare lesion nearly always associated with an underlying breast cancer, clinically impalpable and radiologically undetectable in about 40% of the patients. Fourty-four cases (28 mastectomies and 16 biopsies of the nipple) of Paget's disease of the nipple without clinically and radiologically detectable breast tumor were retrospectively studied by means of histochemistry and immunohistochemistry. Histochemical study showed that Paget cells were PAS positive and diastase resistant, and alcian blue positive at pH 2.5 in 32% and 18%, respectively. Immunohistochemical study showed that Paget cells were EMA and c-erbB-2 positive in 100% and 84%, respectively. Four of the six EMA positive and c-erbB-2 negative cases of Paget's disease of the nipple in which the underlying tumor could be pathologically analyzed were associated with ductal carcinoma in situ of cribriform or mixed types. These findings are helpful for differentiating Paget's disease from other lesions of the nipple, namely Bowen's disease and eczema which do not react with both antibodies, and from nipple adenoma which exhibits a positive staining with anti-EMA antibody and no reactivity with anti-c-erbB-2 antibody.
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PMID:Paget's disease of the nipple without clinically and radiologically detectable breast tumor. Histochemical and immunohistochemical study of 44 cases. 839 88

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

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

Paget's disease of the nipple (PDN) is characterized by Paget's cells infiltrating from an underlying breast carcinoma into the epidermis of the nipple. The tumor cells were reported to overexpress ERBB-2 protein. There is no evidence, whether the overexpression is caused by amplification of the ERBB2 gene (as is the case of invasive duct carcinomas) or by other causes. Because the Paget's cells proliferate vividly we were interested also in cyclin D1 expression and in its relation to the number of CCND1 gene copies. To address these issues, we performed a study using fluorescence in situ hybridization on interphasic nuclei (I-FISH) on formalin fixed / paraffin embedded tissue sections from twelve women with PDN. We compared immunohistochemical (IHC) expression of the ERBB-2 protein and cyclin D1 with the copy number of the gene ERBB2 and CCND1, respectively (I-FISH). In all cases of our series we found overexpression of the ERBB-2 protein (3+), and in all of them there was a strong amplification of the ERBB2 gene (more than 10 signals per a nucleus, usually about 20). Keratinocytes of the epidermis had two signals of the gene. IHC and I-FISH revealed comparable findings in successive biopsies in two patients. Cyclin D1 was positive in seven cases. We found a moderate amplification of the CCND1 gene (up to 10 signals per a nucleus) in three patients only. Any correlation between the cyclin D1 overexpression anda copy number of the CCND1 gene was observed. Combined numerical changes of chromosome 17 and of chromosome 11 were found in seven women. It is concluded that in PDN, the ERBB-2 protein overexpression is caused by amplification of the ERBB2 gene. A specific immuno-therapy with trastuzumab (Herceptin) used in patients with invasive duct carcinoma may be also effective in patients with PDN.
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PMID:Paget's disease of the nipple: a copy number of the genes ERBB2 and CCND1 versus expression of the proteins ERBB-2 and cyclin D1. 1468 59

Paget's disease is a rare form of breast cancer often associated with an underlying ductal carcinoma in situ or invasive cancer. A 47-year-old female patient presented with bleeding from the left nipple since 4 months. Imprint smears from the lesion showed pleomorphic malignant epithelial cells in singles and in small clusters, many of them containing dark brown cytoplasmic pigment granules. There was no palpable breast lump or axillary lymph node enlargement. Based on the physical examination and cytological features, a diagnosis of malignant melanoma with a differential of Paget's disease of the nipple was made. Biopsy showed features of Paget's disease and immunohistochemistry was positive for HER-2/neu, negative for HMB-45 and S-100, thus confirming the diagnosis. This case has been reported to emphasize the fact that Paget's cells can contain imbibed brown cytoplasmic pigment and should not be mistaken for melanoma cells on cytology smears.
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PMID:Pigmented Paget's disease of nipple: A diagnostic challenge on cytology. 2366 48