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)

This study compares the prevalence of elevated serological levels of erbB-2 and myc proteins in 36 breast cancer patients and 25 healthy, ambulatory female controls. The controls were frequency matched to the cases by age and ethnicity. Oncoprotein levels were determined blind to the "case-control status" of the individual from whom the specimen was derived. Corresponding tissue levels were examined in tumors of the 13 cases from whom sufficient tissue was available. Serum oncoproteins were elevated as follows: erbB-2 in one control (4%) compared with nine cases (25%; PFisher's exact = 0.03); myc in no control (0%) compared with seven cases (19%; PFisher's exact = 0.02). Elevated serum levels of erbB-2 or myc oncoproteins were detected in four of the seven cases (57.1%) of in situ cancer without evidence of infiltration. In all cases with elevated serum oncoproteins where tumor tissue was available, the corresponding protein was elevated in the tumor. The three cases who had elevated preoperative serum oncoprotein levels and from whom it was possible to procure postoperative specimens had normal postoperative serum oncoprotein levels. We conclude that (a) erbB-2 and myc oncoproteins are elevated in a proportion of breast cancer patients, (b) the tumor seems to be the source of the serum elevation, and (c) these proteins may be useful as part of a panel of biomarkers of early malignant disease.
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PMID:erbB-2 and myc oncoproteins in sera and tumors of breast cancer patients. 790 81

The authors studied 30 consecutive archival cases of pure breast carcinoma in situ (CIS) for estrogen receptor (ER), progesterone receptor (PR), and c-erbB-2 oncogene product. Clinical factors of age and menstrual status and histologic features of tumor type and nuclear grade were determined. Some 77% represented ductal CIS, with 10% noninvasive papillary, and 13% lobular CIS. A total of 22 of 30 (73%) were ER+ and 19 (63%) were PR+; 24 (80%) were c-erbB-2+ with 11 (37%) showing strong staining; 75% of the ER-PR group had tumors of NG 3, versus 14% for the ER+PR+ plus ER+PR- groups. Nonstatistically significant trends correlating the strongly positive oncogene group with PM status, receptor negativity, and high nuclear grade were noted. The overall rate of receptor positivity, as well as the correlation with nuclear grade, is similar to that in invasive carcinomas c-erbB-2 protein expression shows a higher rate in in situ than is reported for invasive tumors, and shows a tendency to be expressed more strongly in tumors with other features of poor prognosis. Therefore, these factors may also have prognostic significance in CIS. Continued followup of this population to recurrence may provide further insight.
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PMID:Estrogen and progesterone receptor and c-erbB-2 oncoprotein analysis in pure in situ breast carcinoma: an immunohistochemical study. 809 77

In this study we investigated immunohistochemically the expression of p53 and c-erbB-2 proteins in 30 gall bladder adenocarcinomas, one carcinoma in situ, eight gall bladder epithelial dysplasias, and four cases of chronic cholecystitis. p53 expression could be found in 14 (47 per cent) adenocarcinomas and in two out of eight epithelial dysplasias. There were significantly more p53-positive grade II-III tumours than grade I tumours (P = 0.032 according to Fisher's exact probability test). c-erbB-2 expression was found in three (10 per cent) adenocarcinomas, but all dysplasias were c-erbB-2-negative. All three c-erbB-2-positive cases were also p53-positive. The results indicate that p53 mutations and c-erbB-2 gene alterations play a role in the neoplastic transformation of gall bladder epithelial cells. Co-expression of p53 and c-erbB-2 suggests that alterations of these genes might act in concert in the neoplastic transformation. The occurrence of p53 expression in gall bladder dysplasias suggests that p53 mutations could be an early event in the evolution of some gall bladder carcinomas, as has been suggested for some other types of tumours, such as lung squamous cell carcinomas.
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PMID:p53 and c-erbB-2 protein expression in adenocarcinomas and epithelial dysplasias of the gall bladder. 810 Aug 54

Endometrial cancers have been considered to be less prevalent in Japan than in Western countries. However, with the increase in life expectancy, the Westernization of the Japanese diet, and changes in the hormonal environment, the prevalence of the disease has gradually increased even in our country. Similar increases in cancers of the breasts, lungs, colons, and ovaries have been noted in recent years. Much is still unknown regarding the pathogenesis and natural history of endometrial cancer. Although endometrial hyperplasia is considered to be a precancerous lesion of endometrial carcinoma, the relationship between those diseases has not been elucidated to the same degree as that between cervical cancer and cervical dysplasia, or carcinoma in situ. Research findings in genetic oncology have revealed that tumorigenesis involves a multi-step process. It is probable that activation of multiple genes, inactivation of anti-oncogenes, and disappearance of normal inhibitor genes occur in the process of the development of endometrial cancer. The purpose of this study is to elucidate the relationship between oncogenes and the development of endometrial cancer. In addition, the significance of endometrial hyperplasia as a clinical entity is also be evaluated. The roles played by oncogenes in endometrial cancers and endometrial hyperplasias were examined using the most recent molecular biological and immunohistochemical methods. Also, the differences in cellular proliferation and tissue invasiveness were discussed. Results obtained were as follows. Evaluation of cell proliferation (PCNA, FCM) revealed that there was no difference in proliferative activity between atypical hyperplasia and well differentiated adenocarcinoma. Evaluation of oncogene abnormalities (c-myc,c-erbB-2,K-ras,p53) revealed that the development of endometrial cancer was a multistep process involving several oncogenes, as it has been noted in the development of other cancers. Evaluation of extracellular matrix and related factors (cathepsin D, laminin, type IV collagen, tenascin, CD44) showed that tissue invasiveness differed between atypical hyperplasia and well differentiated adenocarcinoma.
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PMID:[Evaluation of the degree of biological behavior in endometrial hyperplasia and endometrial carcinoma: an investigation of proliferative activity, oncogene, and extracellular matrix]. 810 84

Although several morphological and molecular genetic studies have implicated various grades of pancreatic duct hyperplasia as precursor lesions to infiltrating pancreatic adenocarcinoma, the identity of preinvasive pancreatic neoplasms remains controversial. In the present study, the authors examined the expression of the epidermal growth factor receptor homologue, HER-2/neu (c-erbB-2), in pancreatic duct lesions adjacent to infiltrating pancreas cancers in a series of 19 cases of pancreatic duct adenocarcinoma. HER-2/neu expression was examined because it has been identified in a proportion of infiltrating pancreas cancers and because it may provide early neoplasms with a growth advantage over adjacent nonneoplastic epithelium. In normal pancreatic ducts and ductules, HER-2/neu expression was absent in all but one case. By contrast, HER-2/neu was expressed in 82% (P = .008 vs normal ) of ducts with flat mucinous hyperplasia, 86% (P = .03 vs normal) of ducts with papillary mucinous hyperplasia without atypia, 92% (P = .001 vs normal) of ducts with atypical papillary mucinous hyperplasia, and all specimens with carcinoma in situ. HER-2/neu expression was observed in 69% (P = .002 vs normal) of the moderately differentiated infiltrating carcinomas and none of the poorly differentiated infiltrating carcinomas. These data establish HER-2/neu as a potential mediator of growth factor-related signal transduction in pancreatic duct lesions, and provide additional support for the hypothesis that lesions formerly regarded as various grades of hyperplasia instead may represent intraepithelial neoplasms with the potential for subsequent invasion and metastasis.
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PMID:Immunohistochemical evaluation of HER-2/neu expression in pancreatic adenocarcinoma and pancreatic intraepithelial neoplasms. 861 52

Cancer chemoprevention is defined as intervention by chemical agents prior to invasion to inhibit or slow the carcinogenic process. Using surrogate endpoint biomarkers in chemoprevention studies may reduce the size, length and cost of clinical prospective randomized trials in high-risk populations. Intermediate biomarkers are measurable alterations in the tissues at risk and include differentiation, genetic composition, biochemical expression, and proliferation. Assessment is possible because invasive epithelial neoplasms are known to begin as intraepithelial proliferations with a spectrum of cellular abnormalities extending to carcinoma in situ. Genetic heterogeneity begins in the intraepithelial phase; a stochastic accumulation of genetic errors characterizes the progression of clonal evolution within the tumor through the process of invasion and metastasis. Pathologic features associated with this process include tumor classification as well as whether it is intraepithelial or invasive. If the process is intraepithelial, the grade and extent of the intraepithelial lesion are reported. If the neoplasm is invasive, tumor size, extent, degree of differentiation (histologic and nuclear grade), mitotic rate, vascular invasion, and lymph node involvement are evaluated. In assessing biomarkers relevant chemoprevention, and without complete regression of the neoplasm with the chemopreventive agent or agents, measurable parameters along with histopathologic features are applicable. Three methods readily applicable for this purpose that can be applied to paraffin-embedded, formalin-fixed tissue include quantitative pathology, immunohistochemistry, and molecular biologic applications. These methods require some consistency in handling and processing the tissues under study; results may deteriorate due to a number of processing variables, including time to fixation, time in fixative, and fixative type. Quantitative pathology, including static image analysis and flow cytometry, can determine total DNA content. Using static image analysis, very small tumors can be studied. In addition, adjacent intraepithelial and invasive components of a tumor may be studied from a single slide. Steroid receptors, oncogenes, and other proteins detectable through immunohistochemical or molecular biologic methods can be quantitated by this technique as well. Cell cycle synthetic function is assayable by both methods. Flow cytometry can calculate the total percentage of cells in S-phase, or the tumor cell S-phase fraction based on the percentage of cells detected between the G0, G1 peak and the G2 + M peak. A similar approach is generally not applicable with current image analysis equipment; however, cell cycle related proteins such as MIB-1 (Ki-67 associated) can be quantified. Immunohistochemical methods can employ a wide variety of monoclonal antibodies to detect oncogene related proteins, including HER-2/neu (c-erbB-2) and p53. Molecular biologic methods, including in situ hybridization, polymerase chain reaction, and in situ PCR, can have many applications when applied to paraffin-embedded tissues, including detection of viral DNA, identification and measurement of apoptosis, and defining gene deletions.
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PMID:Role of the pathologist in biomarker studies. 874 73

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

Pancreatic intraepithelial neoplasia is only partially defined. Any attempt to establish the diagnostic criteria of early pancreatic carcinoma has been unsuccessful so far. In the present study we investigate expression of HER-2/neu in hyperplastic pancreatic duct epithelium. Material included resected pancreatic tissue obtained from 13 patients with pancreatic carcinoma, 11 with chronic pancreatitis, and 11 patients operated on for other reasons (gastric cancer, carcinoma of papilla Vateri). Hyperplasia of pancreatic duct epithelium was scored as: 1. flat mucosal hyperplasia FH, 2. papillary hyperplasia PH, 3. atypical papillary hyperplasia APH, 4. carcinoma in situ CIS. Immunohistochemical expression of HER-2/neu was studied with the biotin-streptavidin method. Results were scored as: 1+ barely perceptible light membranous rimming, 2+ light to moderate rimming, 3+ moderate to strong rimming. Expression of HER-2/neu paralleled with the hyperplasia grading, in most cases being negative in normal duct epithelium, weak in flat hyperplasia, and moderate to strong in atypical papillary hyperplasia and carcinoma in situ. In conclusion, HER-2/neu expression could be used as an additional marker of hyperplasia, dysplasia and atypia of pancreatic ductal and ductular epithelium in the process of pancreatic epithelial neoplasia. This could be especially useful in the cytological diagnosis of pancreatic intraepithelial neoplasia.
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PMID:HER-2/Neu expression as a progression marker in pancreatic intraepithelial neoplasia. 979 11

Breast cancers arising in women with and without a germline mutation in the BRCA1 or BRCA2 gene display different histological features, which suggests unique mechanisms of molecular pathogenesis: We used a molecular pathological analysis to define the genetic abnormalities relevant to these specific pathogeneses. Tumor material was studied from 40 women with breast cancer diagnosed before 40 years of age, sampled from a population-based study and stratified by BRCA1 and BRCA2 germline mutation status. Cases were not selected for family history or ethnic origin, and none were known to be genetically related. Thus, germline mutation itself is likely to impact on the molecular pathogenesis of these tumors, with no substantial influence due to modifying genetic or environmental factors. Breast cancers occurring in BRCA1 mutation carriers had significantly higher levels of p53 expression, including the preinvasive (carcinoma in situ) stage of disease, compared with cancers occurring in BRCA2 mutation carriers or women with no detectable germline mutation. These cancers also had a higher proliferation rate as measured by Ki-67 antibody. Expression of the prognostic factors c-erbB-2, cyclin D1, and estrogen receptor was significantly less common in BRCA1 mutation carriers. Lower levels of cyclin D1 were also found in cancers from BRCA2 mutation carriers compared with non-mutation carriers. Direct p53 mutation analysis revealed mutations in 18% of all of the early-onset breast cancers within the study and included rare insertion and deletional mutations in cancers from BRCA1 mutation carriers. Our data indicate that a BRCA1 breast cancer phenotype may be recognized by an exceptionally high proliferation rate and early and frequent p53 overexpression but infrequent selection for overexpression of several other prognostic factor proteins known to be involved in breast oncogenesis. In contrast, breast cancers arising in BRCA2 mutation carriers have a more heterogeneous phenotypic profile.
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PMID:Distinct molecular pathogeneses of early-onset breast cancers in BRCA1 and BRCA2 mutation carriers: a population-based study. 1021 14

Downregulation of nm-23 antimetastasis gene has been associated with disease progression in some human tumors. NPD kinase A is the product of the H1 isotype of the nm23 gene and its value as a marker of metastatic potential is well worth investigating. The expression of the nm23-H1 gene peptide was immunohistochemically evaluated in 191 primary mammary cancer tissues. A three-step immunoperoxidase staining procedure was performed and any association of our results with several classical clinicopathologic indicators, including hormonal status and c-erbB-2 oncoprotein membrane immunoexpression, was examined. NDP kinase A-positive cytoplasmic immunolabeling was noticed in 64% of all specimens (123/191) which frequently demonstrated positive progesterone receptor (PgR) status (p = 0.001) and were furthermore characterized by high PgR immunoreactivity rates. This association was significant by both univariate and multivariate statistical analysis. The double nm23-H1 (+)/PgR(+) phenotype was more frequently detected than any other combined phenotype of these markers. The nm23-H1 gene peptide was generally detected in a remarkable proportion of malignant cells, either in the invasive or the intraductal tumor components. Notably, large-cell ductal carcinomas in situ were characterized by lower nm23-H1 immunoreactivity rates when compared with other in situ cancer types. Quantitatively increased nm23-H1 immunopositive staining was more frequently observed in special histologic types of infiltrating cancers, in high nuclear grade tumors, as well as in carcinomas with high PgR levels (p = 0.05). The nm23-H1 (-)/c-erbB-2(+) phenotype was more often detected in the cancers of this study than the nm23-H1(+)/c-erbB-2(+) one. The former phenotype was correlated to postmenopausal ages as well as to extensive axillary nodal involvement by univariate statistical analysis. It is noteworthy that nm23-H1(-) status, on its own, was not statistically associated either with the presence or with a high number of involved lymph nodes. On the contrary, nm23-H1 immunopositivity was, paradoxically, more frequently observed in tumors of relatively increased TN tumor stage. Tumor progression is thus more likely to depend on the c-erbB-2 gene's overexpression. Possibly, any favorable outcome in nm23-H1(+) cases might be due to the fact that they also express PgR, which is a marker of a more functionally differentiated phenotype.
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PMID:Nm-23, c-erbB-2, and progesterone receptor expression in invasive breast cancer: correlation with clinicopathologic parameters. 1040 1


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