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

The distribution of several markers of keratinocyte differentiation was studied in normal epidermis, basal cell carcinomas (BCCs), and squamous cell carcinomas (SCCs) using the immunoperoxidase technique on frozen sections of punch biopsy specimens. As markers a panel of chain-specific monoclonal antibodies (MoAbs) directed against cytokeratin (CK) 4, 8, 10, 13, 18 and 19, a polyclonal antiserum against involucrin, as well as a MoAb against the epidermal growth factor (EGF) receptor were used. In 15 out of 19 BCCs tested, expression of CK 8 was seen. Only a few individual cells in a limited number of BCCs showed positive staining for CK 4, 18, or 19. No expression of CK 10 was seen except for some foci of cell keratinization. Involucrin was not found in BCCs except for some squamous horn cysts. In all BCC cells expression of EGF receptor was found. In the suprabasal layers of normal epidermis from SCC patients, positive staining for CK 10 was seen. A few individual cells in a limited number of SCCs showed positive staining for CK 4, 8, or 18. Involucrin was expressed in the center of SCCs and in the upper layers of normal epidermis. Expression of EGF receptor was found in all SCC cells. These results demonstrate differences in cellular origin and differentiation between BCC and SCC.
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PMID:Expression of EGF receptor, involucrin, and cytokeratins in basal cell carcinomas and squamous cell carcinomas of the skin. 247 80

Fifty-three solid and 33 fine-needle aspirate (FNA) samples (20 paired) of human breast carcinomas were examined by flow cytometry. Experiments were conducted to assess whether FNA samples were phenotypically representative of the solid tumour. Quantification of oestrogen receptor (ER), epidermal growth factor receptor (EGFR), c-erbB-2 receptor levels and ploidy were examined on the total and cytokeratin-positive cell populations. The absolute number of molecules of cytokeratin per cell expressed on the FNA (n = 33) and solid tumour (n = 53) samples showed no significant difference, but, on a proportional basis, there was a significant difference between the two samples (P = 0.004), with lower expression exhibited by the FNAs. Examination of paired data showed no significant difference in the percentage of cytokeratin-positive cells (P = 0.51) or in the number of cytokeratin molecules expressed (P = 0.25). While the correlation for ER expression between paired tumour and FNA samples in the absence of cytokeratin gating was P = 0.06, r2 = 0.18, clear correlation was shown when a cytokeratin gate was used (P = 0.005, r2 = 0.4). Repeating this experiment for EGFR, it was found that no correlation was seen between FNA and solid tumour (P = 0.2, r2 = 0.14) in ungated populations, but use of the cytokeratin gate improved the correlation (P = 0.05, r2 = 0.3). A similar finding was seen with c-erbB-2 expression (P = 0.2, r2 = 0.1) without cytokeratin gating and when it was employed (P = 0.05, r2 = 0.4). Ploidy data showed concordance in 18/20 cases. Three cases of aneuploidy were missed by FNA, and this was because of an insufficient number of cells for analysis. The presented data suggest that FNAs are representative of solid tumours and may be useful for measuring receptor levels on clinical material when cytokeratin gating is used. However, observation by light microscopy is still necessary to confirm the presence of tumour cells in FNAs subjected to flow cytometry.
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PMID:Are fine-needle breast aspirates representative of the underlying solid tumour? A comparison of receptor levels, ploidy and the influence of cytokeratin gates. 754 18

A novel technique in multiparameter flow cytometry (FCM) using dual laser excitation of three fluorescent dyes has been developed to differentiate breast epithelial cells from stromal components. This technique has been applied to determine the expression of the oncoprotein c-erbB-2 in breast epithelial tumors. SK-BR-3, a breast cancer cell line with c-erbB-2 overexpression, can be identified by FCM from a mixed cell suspension using a monoclonal anti-human cytokeratin antibody conjugated with fluorescein isothiocyanate. Using the mouse monoclonal anti-c-erbB-2 antibody, TA-1 (4.8 +/- 1.0 x isotype control), the c-erbB-2 oncoprotein overexpression in breast epithelial cells can be detected as an increase in indirect blue fluorescence by aminomethyl coumarin. MCF-7, a breast cancer cell line with normal c-erbB-2 expression, has baseline blue fluorescence (1.0 +/- 0.5 x isotope control). Twenty-one fresh breast specimens have been examined by FCM. Overexpression of c-erbB-2, defined by blue fluorescence ratio of TA-1/isotype control > or = 1.5 (> 3 SD from baseline), is detected in 0 of 3 patients with Stage I cancer, 5 of 14 patients with Stage II and III cancer, and 3 of 4 patients with proliferative disease. Patients with elevation of oncoprotein detected by FCM have corresponding RNA overexpression detected by Northern blot hybridization and increased gene amplification detected by Southern blot hybridization. FCM allows for the simultaneous identification of breast epithelial cells and the selective examination of these cells for the expression of c-erbB-2 oncoprotein, thus minimizing stromal contamination. This represents a novel application of FCM with potential for wide clinical applicability.
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PMID:Detection of c-erbB-2 oncoprotein expression in breast tissue by multiparameter flow cytometry. 768 35

We recently established a new human breast cell line, designated KPL-1, which was derived from the malignant effusion of a patient with breast cancer. This cell line is highly tumorigenic and grows rapidly in female nude mice. Cytogenetic analysis indicated its human origin and revealed a hypertriploid modal number of chromosomes. Electron microscopic examination suggested that the KPL-1 cells are of epithelial origin. Immunohistochemical studies revealed that the cells express cytokeratin, carcinoembryonic antigen and CA 15-3. They also possess a large number of oestrogen receptors but not progesterone receptors. Interestingly, KPL-1 cells seem to grow oestrogen independently in vitro. No amplification of c-erbB-2, c-myc, H-ras and N-ras genes was detected. KPL-1 cells secrete a large amount of tissue polypeptide antigen (TPA). Although the secretion of CA 15-3 seemed to be constant throughout all cell growth phases, TPA secretion increased during the exponential growth phase and decreased during the plateau phase. Serum TPA levels significantly correlated with the volume of KPL-1 tumours transplanted into nude mice. These data suggest that this KPL-1 cell line may be useful for studying oestrogen-independent growth and the kinetics of tumour-associated antigens in vivo as well as in vitro.
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PMID:A new human breast cancer cell line, KPL-1 secretes tumour-associated antigens and grows rapidly in female athymic nude mice. 771 Sep 53

A case of extramammary Paget's disease of the axilla in an 84-year-old patient is presented. No underlying carcinoma was found and the lesion was treated successfully by wide local excision. Immunohistochemical staining showed nuclear immunoreactivity for c-myc and cytoplasmic staining for CEA, EMA, CAM 5.2, EGRF, c-erbB-2 and pan-cytokeratin in all the Paget cells. No immunoreactivity of the lesion was observed for S-100 protein, pan-ras, H-ras, K-ras, and p53 oncoproteins. Further research is needed to establish whether oncoprotein overexpression plays a role in the pathogenesis of extramammary Paget's disease and can be used as a diagnostic or prognostic marker.
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PMID:Extramammary Paget's disease of the axilla. 807 May 99

In order to assess the specificity of biotinylated anti-c-erbB-3 antibody, screening was performed on a series of tumour cell lines and lymphocytes. Staining was found to be consistent, with good reproducibility. Twenty-nine consecutive breast cancer samples were obtained from women treated with tamoxifen and undergoing elective mastectomy. Twenty-eight invasive ductal carcinomas and 1 DCIS were stained for c-erbB-3 expression: 2 were grade I (Bloom and Richardson), 15 grade II, and 11 grade III tumours, 1 being unclassified; 16 were axillary node positive and 10 node negative; in 2 cases no nodes were sampled. Tumours examined by flow cytometry were stained with cytokeratin FITC antibody and the cytokeratin-positive population gated. Using Mann-Whitney analysis no association was seen between c-erbB-3 expression and Bloom and Richardson grade or axillary node status. In the tumour samples c-erbB-3 expression was found to show as association with EGF-R (P = 0.021 r2 = 0.16), PgR (P = 0.02, r2 = 0.16), c-myc (P < 0.0001, r2 = 0.5), c-jun (P = 0.001, r2 = 0.4) and c-fos (P = 0.001, r2 = 0.5) but not with c-erbB-2 (P = 0.2, r2 = 0.06), ER (P = 0.4, r2 = 0.02) or p53 1801 (P = 0.05, r2 = 0.2). Expression of c-erbB-3 may not be an independent marker of prognosis, but it is associated with other markers of poor prognosis and early cellular events linked with aberrant growth and differentiation.
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PMID:A flow cytometric study of c-erbB-3 expression in breast cancer. 853 73

c-erb B2/neu has been demonstrated to be a transforming oncogene in both rodent and human prostatic epithelial cells. To understand the potential role of neu in human prostatic cancer progression, we used a transfer procedure to determine whether neu amplification/overexpression leads to increased tumor growth and metastasis. We chose an androgen-independent human prostatic epithelial cell line, PC-3, as the target for gene transfer. PC-3 cells were cotransfected with pSVneu-T (a point-mutated rat neu oncogene construct) and pSV2neo, and single-cell cloned. Fifty cell clones were isolated and characterized, of which two neu-transfected clones (N17 and N35) and a neo control clone (C32) were studied extensively with respect to neu gene integration, levels of neu mRNA and protein expression, anchorage-independent growth, and tumorigenic and metastatic potential. Results showed that: 1) Clone N35 contained 70 copies of the neu oncogene and a high level of neu mRNA transcripts. It acquired increased anchorage-independent growth potential in vitro and increased tumorigenicity in vivo. 2) Clone N17 contained 10 copies of the neu oncogene and a low level of neu mRNA transcripts. It did not acquire additional capability for anchorage-independent growth and tumorigenic potential as compared to the controls. 3) Despite an increased level of neu mRNA transcripts present in clone N35, there was no corresponding increase of the steady-state levels of neu protein in this particular clone. 4) When administered subcutaneously, none of the cell clones tested, including the control neomycin-resistant clone, acquired metastatic potential. However, clone N35 exhibited marked metastatic potential when administered orthotopically; this cell clone was found to disseminate widely to the lymph nodes, kidney, skeletal muscle, lung, liver, and bone. 5) When neu-transfected cell subclones from N35-induced primary and metastatic lymph node, kidney, and bone tumors were analyzed for cytoskeletal, extracellular matrix, and cell adhesion protein expression, the bone metastatic subclone exhibited increased levels of vimentin and collagen IV and decreased levels of cytokeratin and ICAM-1. These results, taken together, suggest that neu transfection induces secondary changes, which, rather than neu protein per se, are responsible for the acquisition of tumorigenic and metastatic potential of prostate cancer cells when an appropriate host microenvironment is present.
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PMID:Transfected neu oncogene induces human prostate cancer metastasis. 860 95

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

Ninety-four cases of early abortion have been studied. Five histological groups of lesion have been identified by routine histological techniques on abortion materials, group I corresponding to partial hydatidiform mole. Cytogenetic analyses have revealed chromosome anomalies in near 50% of cases with a prevalence of triploidies followed by trisomies and monosomies. Normal histological findings are more often associated with normal karyotypes and group I with abnormal karyotypes but a specific correlation between histological pattern and cytogenetic anomalies is lacking. Neither some histochemical reactions nor the well preserved immunohistochemical reactivities of beta-hCG, hPL, PLAP, AFP, cytokeratin, vimentin, desmin, factor VIII, CD 68, MIB1 (growth fraction), EGF-R, p53 and c-erbB-2 oncoproteins have disclosed specific chromosome anomalies. They have only allowed a better definition of histological groups. A simple histological evaluation, although extended to immunohistochemical reaction may not substitute the cytogenetic analyses, not even for purposes of preselection.
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PMID:[Correlation of the histological and cytogenetic pictures in placental tissue from early abortion. Does immunohistochemistry have a role?]. 900 96


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