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)

Among the various factors reported as having significant prognostic value in primary breast cancers, the author discusses the value of well established "classical" prognostic factors used routinely and "new" prognostic factors developed over recent years as a result of progress in cell and molecular biology. The presence of axillary lymph node metastases remains the most important prognostic factor of recurrence, justifying post-surgical adjuvant therapy. However, in patients with negative axillary nodes (N-), the size of the tumour, Scarff-Bloom-Richardson (SBR and MSBR) histological grade, certain particular histological types (carcinoma in situ and tubular, colloid or pure papillary cancer) and hormone receptors (ER and PR) appear to be well established prognostic factors allowing the identification, within this group of N- patients who generally have a good prognosis, those patients with a low risk of recurrence and therefore not requiring adjuvant therapy. In contrast, the proliferative activity (ploidy and S phase, Thymidine Labeling Index, antibody Ki67), cathepsin D, thymidine kinase, EGF receptors, several genes including oncogene HER-2/neu, are recently developed prognostic factors whose significance needs to be confirmed by further studies.
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PMID:[Prognostic factors in breast cancer]. 134 Jan 64

The structure and expression of the proto-oncogene c-erbB-2 was studied in 86 patients with transitional cell carcinoma. Initial tissue samples comprised 37 grade 1, 32 grade 2 and 13 grade 3 tumours and four cases of carcinoma in situ. At the time of this first tumour sample, amplification of the c-erbB-2 gene was demonstrated by Southern blotting in 1/37 grade 1, 5/32 grade 2 and 6/13 grade 3 tumours (0.005 less than P less than 0.01). Tumour 're-occurrences' were obtained from 23 of these patients on one or more occasions. Amplification was detected in re-occurrences from seven of these 23, none of whom showed amplification in the first tumour sample. DNA was also extracted from exfoliated cells in urine collected from five cases of carcinoma in situ and c-erbB-2 amplification was demonstrated in one of these. No gene amplification was identified in patients' lymphocytes, ten biopsies of normal urothelium and 22 various intravesical pathologies. Increased expression of c-erbB-2 mRNA correlated with amplification of the gene. In addition, raised levels of mRNA were seen in the absence of gene amplification in six tumours. Immunoblotting using the polyclonal antibody 21N, raised against the c-terminus of the c-erbB-2 protein demonstrated increased amounts of a 185 kD immunoreactive protein in tumours with increased c-erbB-2 gene copy number compared with control tissues. In some tumours with high c-erbB-2 gene copy number, a 155 kD immunoreactive protein not detected in controls was expressed at higher level than the 185 kD protein. Immunocytochemistry using a monoclonal antibody AB-3, raised against the c-terminus of the c-erbB-2 protein, showed a positive reaction in the cytoplasm and cell membrane of tumours with gene amplification and in 40% of tumours with no amplification. An association was found between c-erbB-2 amplification and over-expression and the development of tumour re-occurrences. We suggest that c-erbB-2 amplification and over-expression may provide a useful molecular marker in transitional cell carcinoma of the bladder and merits further investigation as a potential prognostic indicator.
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PMID:Amplification and over-expression of c-erbB-2 in transitional cell carcinoma of the urinary bladder. 167 27

Amplification of the HER-2/neu proto-oncogene in breast cancer has been reported to correlate with poor patient prognosis. The proliferation, or growth fraction, of cells has also been shown to be of prognostic importance in breast cancer. A study was conducted to evaluate the correlation between HER-2/neu gene expression and proliferation in breast cancer. Quantitative immunohistochemical methods for the detection of the HER-2/neu protein expression and for assessing the proliferation fraction on frozen sections of tumor cells were used. The detection of epidermal growth factor receptor (EGFR) along with quantitative DNA ploidy analysis, also was performed on the same breast cancers. The results indicated two subgroups of invasive ductal carcinoma; 1) HER-2/neu overexpressing cases that were negative for EGFR expression and had low proliferation fraction, and a tetraploid DNA pattern (22 cases), and 2) other combinations of HER-2/neu expression and EGFR expression, with a high proliferation fraction and an aneuploid DNA pattern (38 cases). Eight cases of carcinoma in situ were positive for HER-2/neu overexpression and negative for EGFR expression, and had a high proliferation fraction and a tetraploid DNA pattern. Twenty-six cases of low-grade carcinoma exhibited low proliferation and a diploid DNA pattern.
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PMID:HER-2/neu oncogene expression and proliferation in breast cancers. 197 97

Monoclonal antibodies were used to localize immunohistochemically epidermal growth factor receptor and HER-2/neu in normal and neoplastic frozen tissue samples from the lower genital tract of women. In squamous epithelia of the cervix, vulva, and vagina, epidermal growth factor receptor and HER-2/neu both were expressed most strongly by basal keratinocytes. Expression of both of these cell surface molecules decreased as cells underwent differentiation toward the mucosal surface. In contrast, both epidermal growth factor receptor and HER-2/neu were expressed throughout the entire thickness of the epithelium by undifferentiated squamous cells in squamous metaplasia, raised condyloma, and carcinoma in situ. In 34 squamous cancers of the cervix, vulva, and vagina, all malignant cells were found to have moderate to heavy staining for epidermal growth factor receptor. Staining of 33 of these cancers for HER-2/neu was light, although one patient who presented with distant metastases had heavy staining for HER-2/neu. These data suggest that although overexpression of HER-2/neu in squamous cancers of the lower genital tract is a rare event, it may be associated with aggressive biologic behavior.
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PMID:Expression of epidermal growth factor receptor and HER-2/neu in normal and neoplastic cervix, vulva, and vagina. 197 42

Seventy specimens of normal endometrium (n = 13) and cervix (n = 12), endometrial hyperplasia (n = 4), cervical dysplasia (n = 20), endometrial (n = 11) and cervical carcinoma (n = 8) and uterine metastases of mammary carcinomas (n = 2) have been analysed for c-erB-2 expression with immunohistochemistry employing a monoclonal anti ERBB-2 antibody and Northern-blot hybridization using single stranded RNA probes. In comparison with the c-erbB-2 mRNA expression level found in normal samples, two advanced and poorly differentiated endometrial adenocarcinomas (FIGO IV) and two ductal mammary carcinomas which had metastasized to the uterus, together with three carcinomas in situ of the cervix, showed c-erbB-2 enhanced transcription level. All other endometrial samples including adenomatous hyperplasia and nine endometrial carcinomas (FIGO I), and all other lesions of squamous epithelial origin displayed transcriptional activities at or below the baseline level. Immunohistochemical study of ERBB-2 protein expression showed staining in most samples, although different in distribution and intensity. Staining of endometrial glands was seen in unevenly distributed cells or cell clusters. In contrast, for endocervical glands, labelling was observed distinctly on basally located cells (reserve cells) and at the subapical side of luminal cells. Faint labelling of the basal cell layer was also observed in squamous epithelia. It was more pronounced in severe cervical dysplasia and carcinoma in situ. In carcinomas of glandular origin, dedifferentiation was accompanied by an increase in cytoplasmic labelling, whereas the intensity of staining was not related to differentiation in squamous cell carcinomas. While data derived from Northern blots are suggestive of c-erbB-2 overexpression to indicate an advanced and dedifferentiated state of tumours of glandular origin, staining with an anti-ERBB-2 antibody occurred in both normal and atypical squamous and glandular epithelia and may indicate regular proliferation and/or differentiation-associated events.
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PMID:Immunohistochemical investigation and northern blot analysis of c-erB-2 expression in normal, premalignant and malignant tissues of the corpus and cervix uteri. 198 Jan 67

The purpose of this study was to characterize the clinical and histological features of intraoral squamous cell carcinoma in men who were seropositive for the human immunodeficiency virus and to evaluate viral cofactors (human papillomavirus, herpes simplex virus, Epstein-Barr virus), proliferative index (proliferating cell nuclear antigen), a factor associated with invasion (cathepsin D), and mutated tumor suppressor gene and proto-oncogene products (mutated p53, c-erbB-2). Four men who were seropositive for the human immunodeficiency virus and had acquired immunodeficiency syndrome presented with painful oral lesions of variable duration. Oral cancer risk factors included heavy tobacco use (four of four), heavy alcohol use (three of four), and previous radiotherapy (one of four). The lesions consisted of ulcers (two of four), a fungating mass (one of four), and papillary erythroplakia (one of four). Incisional biopsy specimens were obtained. High-stringency in situ hybridization was performed with DNA probes to the human papillomavirus (types 6/11; 16/18; 31/33/35) and Epstein-Barr virus: Immunocytochemical studies for the herpes simplex virus, proliferating cell nuclear antigen, cathepsin D, mutated p53, and c-erbB-2 were performed. Two lesions were moderately differentiated squamous cell carcinoma, one lesion was a basaloid squamous cell carcinoma, and one was carcinoma in situ. Stage of disease at diagnosis was II (one of four), III (two of four), and IV (one of four). Three cases were positive for the human papillomavirus, one case was positive for Epstein-Barr virus, and three cases were positive for the herpes simplex virus. C-erbB-2 was focally positive in one case, and mutated p53 was positive in a separate case.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraoral squamous cell carcinoma in human immunodeficiency virus infection. A clinicopathologic study. 755 63

Frequent recurrences and multicentricity of bladder cancer suggest that alterations of the urothelium distant from the tumor may be relevant to prognosis. In this study immunohistochemistry and fluorescence in situ hybridization (FISH) were used to examine expression of p53, erbB-2, and epidermal growth factor receptor (EGF-r), genomic aberrations, and tumor cell proliferation (Ki67 LI) in normal and dysplastic urothelium. Biopsy specimens examined included normal urothelium (n = 40), mild dysplasia (n = 34), moderate dysplasia (n = 18) and carcinoma in situ (CIS; n = 20). Several different oncogene expression patterns were found, only some of which were associated with dysplasia. EGF-r expression was equally frequent in normal and dysplastic urothelium and showed a strong association with Ki67 LI (P < .0001). A purely superficial erbB-2 positivity was present in both normal and dysplastic biopsies. However, diffuse erbB-2 positivity and p53 overexpression were both associated with advanced dysplasia (P < .0001 each). FISH analysis showed erbB-2 gene amplification and p53 deletions in selected CIS, as well as a marked chromosome 17 copy number heterogeneity in all six CIS examined. These findings indicate a considerable genomic instability in bladder CIS. They show that both erbB-2 and p53 are altered during malignant transformation. Detectable oncogene expression alone, however, is not diagnostic of malignancy in bladder urothelium.
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PMID:Patterns of p53, erbB-2, and EGF-r expression in premalignant lesions of the urinary bladder. 767 97

In a patient with non-palpable breast carcinoma, c-erbB-2 gene amplification was detected by means of polymerase chain reaction (PCR) in the small number of breast carcinoma cells present in nipple discharge. Amplification of the c-erbB-2 gene is more frequent in carcinoma in situ than in invasive types. Detection by a PCR-based method may help diagnose non-palpable breast carcinoma with nipple discharge. Since this gene amplification is related to high proliferation, it might provide useful preoperative information regarding intraductal carcinoma of comedo type and predict responses to chemotherapy.
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PMID:Detection of c-erbB-2 gene amplification in nipple discharge by means of polymerase chain reaction. 774 37

Intraductal papillary growth of mucin producing hypersecreting, columnar cells characterizes a group of rare pancreatic exocrine neoplasms which we propose to call intraductal papillary-mucinous tumors (IPMT). We analysed the histopathology of 26 IPMT in relation to gastro-enteropancreatic marker expression, genetic changes and biology. Four IPMT showing only mild dysplasia were considered to be adenomas. Nine tumours displayed moderate dysplasia and were regarded as borderline. Severe dysplasia-carcinoma in situ changes were found in 13 IPMT which were therefore classified as intraductal carcinomas. Six of these carcinomas were frankly invasive and two of these had lymph node metastases. The invasive component resembled mucinous non-cystic carcinoma in all but one tumour which showed a ductal invasion pattern. Immunohistochemically, an intestinal marker type was found in most carcinomas, while gastric type differentiation prevailed among adenomas or borderline tumours. K-ras mutations (seven at codon 12 and one at codon 13) were found in 31% of IPMT (2 adenomas, 1 borderline, 5 carcinomas). Nuclear p53 overexpression was detected in 31% of IPMT (6 carcinomas and 2 borderline IPMT) and correlated with p53 mutations (one at exon 8 and the other at exon 5) in two carcinomas. p53 abnormalities were unrelated to K-ras mutation. c-erbB-2 overexpression was observed in 65% of IPMT, with various grades of dysplasia. Twenty-two of 24 patients are alive and well after a mean post-operative follow-up of 41 months. Only two patients, both with invasive cancer at the time of surgery, died of tumour disease. It is concluded that pancreatic IPMT encompass neoplasms which, in general, have a favorable prognosis, but are heterogeneous in regard to grade of dysplasia and marker expression. Adenoma, borderline tumour, intraductal carcinoma and invasive carcinoma can be differentiated. p53 changes but not K-ras mutation or c-erbB-2 overexpression are related to the grade of malignancy. Most IPMT differ in histological structure, marker expression and behaviour from ductal adenocarcinoma.
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PMID:Intraductal papillary-mucinous tumours represent a distinct group of pancreatic neoplasms: an investigation of tumour cell differentiation and K-ras, p53 and c-erbB-2 abnormalities in 26 patients. 782 Mar

One hundred and nine primary breast cancers were analyzed to assess the presence of the HER-2/neu gene product (p185), the oestrogen (ER) and the progesterone (PR) receptors, and the total cathepsin D status. An enzyme-linked immunosorbent assay (ELISA kit, Oncogene Science Inc.) was used for the evaluation of p185 in pellets obtained after a 100,000 x g centrifugation, ER and PR were measured by enzyme immunoassay (EIA kit, Abbott Laboratories), and the total cathepsin D content was evaluated by immunoradiometric assay (IRMA kit, CIS Biointernational). We showed that the ELISA kit is feasible to quantify the p185 present in breast cancer cell membranes, and that the detector antibody recognises a protein of apprroximatly M(r) 185,000. The detected antigen was inversely related to both ER and PR, but it did not correlate to total cathepsin D. No significant differences were found in the expression of p185, ER, PR, cathepsin D between infiltrating ductal carcinomas without special features (NOS) and non-ductal (non-NOS) carcinomas. Nevertheless, in NOS carcinomas, a trend was observed in the p185 levels expressed by the tumours with different histological grades, in that p185 concentration was higher in the poorly differentiated grade 3 with respect to grade 2 and grade 1.
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PMID:Enzyme-linked immunosorbent assay of HER-2/neu gene product (p185) in breast cancer: its correlation with sex steroid receptors, cathepsin D and histologic grades. 790 96


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