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)

AIMS--To investigate overexpression of the oncoprotein c-erbB-2 in the dysplasia/carcinoma sequence of Barrett's columnar-lined oesophagus (CLO). METHODS--Immunohistochemical staining was performed using the monoclonal antibody NCL-CB-11 on formalin fixed tissue from 31 cases of Barrett's carcinoma, 20 cases of cancer associated dysplastic CLO, seven cases of dysplastic CLO without cancer, and 20 cases of non-dysplastic CLO. Membranous staining was regarded as positive for c-erbB-2 overexpression; cytoplasmic staining was recorded separately as its significance is uncertain. RESULTS--Membranous c-erbB-2 overexpression was observed in eight of 31 (26%) carcinomas and in none of the cases of dysplastic CLO. Variable cytoplasmic staining was seen in four of 31 (13%) tumours and seven of 27 (26%) cases of dysplastic CLO. No staining was observed in non-dysplastic CLO. CONCLUSIONS--C-erbB-2 overexpression is a relatively late event in the development of some Barrett's carcinomas and is unlikely to be involved in the early stages of neoplastic transformation of CLO.
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PMID:c-erbB-2 overexpression in the dysplasia/carcinoma sequence of Barrett's oesophagus. 774 11

Esophageal cancer is one of the 10 most prevalent human cancers worldwide. The incidence of esophageal adenocarcinoma is on the rise and patients with this disease typically have very poor prognosis. Informative biomarkers would benefit the clinical management of this disease. We examined 13 cases with esophageal adenocarcinomas and 5 cases with Barrett's esophagus for amplification of the EGFR and erbB-2 genes. We detected multiple copies of the EGFR gene in 30.8% of the tumors and multiple copies of the erbB-2 gene in 15.4% of the tumors. Of the cases with amplification of the erbB-2 gene, co-amplification of the EGFR gene was found. Multiple copies of the EGFR gene were also found in one case of Barrett's esophagus. Immunohistochemical staining of the tissues revealed increased expression of the erbB-2 protein in Barrett's mucosa and adenocarcinoma, but no associations between staining intensity and degree of EGFR or erbB-2 gene amplification, histology, or tumor stage were found. Differential polymerase chain reaction was examined as a method for pre-operative detection of gene amplification in esophageal tumors and Barrett's mucosa.
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PMID:Amplification and over-expression of the EGFR and erbB-2 genes in human esophageal adenocarcinomas. 809 13

We sought to determine if an immunohistochemical panel of p53, PCNA, and c-erbB-2 was a useful biomarker of transformation in Barrett's metaplasia. P53, PCNA, and c-erbB-2 immunohistochemistry was performed on resected Barrett's specimens selected to show discrete grades of dysplasia and then on prospectively obtained biopsies. In resection specimens, p53 was positive in 36% with no dysplasia, in 30% with low-grade dysplasia, in 85% with high-grade dysplasia, and in 90% of adenocarcinomas. While an evaluation of proliferation throughout the specimen did not differ between groups, surface proliferation was significantly higher in high-grade dysplasia than in low-grade or no dysplasia. All high-grade dysplasia specimens were positive for at least one marker, compared to 44% with no or low-grade dysplasia. C-erbB-2 was only seen in 31% with high-grade dysplasia and in 10% of adenocarcinomas. Prospectively, the panel had a sensitivity of 100%, a specificity of 81% and an overall accuracy of 83% in identifying patients who developed high-grade dysplasia or cancer. Thus, overexpression of p53 occurs early in the malignant transformation of Barrett's and increases with histologic progression, and proliferation at the surface of Barrett's epithelium increases with progressive grades of dysplasia. An immunohistochemical panel of p53 and PCNA is a useful biomarker for Barrett's metaplasia.
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PMID:Expression of p53, PCNA, and C-erbB-2 in Barrett's metaplasia and adenocarcinoma. 944 Jun 19

Barrett's esophagus, or specialized intestinal metaplasia, is a common condition associated with gastroesophageal reflux and an increased risk for adenocarcinoma of the esophagus and gastric cardia. Currently, clinical surveillance for early detection of adenocarcinoma relies on the histopathological assessment of dysplasia. In this review we present data from the published literature, and combine this with results from our own research, to address what is currently known about the environmental factors and the molecular changes thought to be important in the pathogenesis of Barrett's esophagus. The most important and well-characterized molecular changes, preceding the development of dysplasia, are alterations in the p53 and erbB-2 genes and aneuploidy. These molecular changes, as well as environmental influences, such as the quality and quantity of gastroduodenal refluxate, may result in abnormal cell proliferation which in turn promotes further genetic abnormalities and deregulation of cell growth. The identification of molecular changes, in the context of predisposing environmental factors, will enhance our understanding of the malignant progression of Barrett's esophagus leading to more effective surveillance and treatment.
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PMID:Recent developments in the molecular characterization of Barrett's esophagus. 957 72

Limited information is currently available on chromosomal abnormalities in esophageal adenocarcinoma and associated premalignant lesions. In this study, numeric changes affecting chromosomes 4, 6, 7, 8, 9, 10, 11, 12, 17, 18, X, and Y were analyzed by using fluorescence in situ hybridization (FISH) with chromosome-specific centromere DNA probes in 12 esophageal adenocarcinomas. In addition, TP53 overexpression, measured by immunohistochemistry, and amplification of HER-2/neu and C-MYC, detected by FISH, were analyzed within the same tumors. The most common numeric abnormalities detected were gains of chromosomes 12 (8 cases), 6 (7 cases), 7 (7 cases), and 11 (6 cases). The total number of abnormal chromosomes varied from 0 to 10, with an average of 4.6 per case. Overexpression of TP53 was present in 9 of 12 cases. No correlation was noted between the degree of aneusomy and TP53 overexpression. In contrast, HER-2/neu amplification was present in two cases, both with large numbers of aneusomic chromosomes. Amplification of C-MYC was detected in only one case that had a moderate number of numeric abnormalities. In a subset of cases in which premalignant lesions were examined, aneusomy was found to be an early change, frequently present in both Barrett's esophagus and dysplastic regions. In contrast, gene amplification and TP53 overexpression were restricted to more advanced areas of dysplasia and malignancy. Screening larger cohorts of patients with Barrett's esophagus or dysplasia for numeric abnormalities of chromosomes 6, 7, 11, and 12 may determine whether any of these abnormalities are predictive markers of progression to malignancy.
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PMID:Interphase cytogenetics of esophageal adenocarcinoma and precursor lesions. 977 3

Patients with Barrett's columnar-lined esophagus are at increased risk of developing esophageal adenocarcinoma, the incidence of which has increased rapidly especially in the USA. Although the number of patients with Barrett's adenocarcinoma is fewer in Japan than in the USA, all gastroenterologist should know its multistep carcinogenic process. Tumor suppressor genes (p53, p16), oncogenes (c-erbB-2, H-ras, K-ras, cyclin D1, src), and growth factor/receptor (TGF-alpha, EGFR) seem to cause the malignant transformation of Barrett's esophagus. Because detection of these molecular alterations is feasible, more accurate diagnosis of Barrett's esophageal biopsy specimens should be made by adding the molecular examination to the conventional pathologic examination.
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PMID:[Molecular alterations in Barrett's esophagus and adenocarcinoma]. 1037 32

The HER-2/neu oncogene is localized to chromosome 17q and shares significant homology with the epidermal growth factor receptor. HER-2/neu protein overexpression has been associated with poor prognosis in a variety of tumors, but its significance in Barrett's esophagus-associated adenocarcinoma (BEAd) is unknown. Therefore, the aim of this study was to evaluate the prevalence and prognostic value of HER-2/neu gene amplification by fluorescence in situ hybridization (FISH) in 63 cases of BEAd. Routinely processed tissue sections from resection specimens of 63 patients with BEAd (M/F ratio, 10:1; mean age, 63 years) were assayed for HER-2/neu gene amplification by FISH using the Ventana unique sequence probe (Ventana Medical Systems, Inc, Tuscon, AZ). FISH results were correlated with the pathological features of the tumors and with patient survival. Clinical follow-up data were available for 54 patients (mean follow-up, 31 months [range, 1 to 152 months]). The HER-2/ neu gene was amplified in 12 of 63 (19%) cases. The presence of HER-2/neu gene amplification showed a trend toward a correlation with depth of tumor invasion (P = .07), lymph node metastasis (P = .13), and pathological stage (P = .14), but did not correlate with any of the other pathological features, such as degree of differentiation or tumor size. On both univariate and multivariate analysis, HER-2/neu gene amplification was associated with shortened survival (P = .03). HER-2/neu oncogene amplification, as determined by FISH, correlates with shortened patient survival and independently predicts poor outcome in patients with BEAd.
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PMID:HER-2/neu gene amplification by FISH predicts poor survival in Barrett's esophagus-associated adenocarcinoma. 1066 10

To characterize cytogenetic alterations found in Barrett's adenocarcinoma (BA) and, more importantly, its premalignant stages, we studied chromosomal imbalances in various lesions in the histologically proposed metaplasia-dysplasia-carcinoma sequence using comparative genomic hybridization (CGH). Using 30 esophageal adenocarcinoma resection specimens, we were able to study 30 areas of Barrett's adenocarcinoma and 8 lymph node metastases (LN). In addition, we investigated 25 premalignant lesions adjacent to BA derived from a subset of 14 resection specimens including 11 areas of high grade dysplasia (HGD), 8 areas of low grade dysplasia (LGD), and 6 areas of intestinal metaplasia (IM), which were laser-microdissected and studied with CGH. To validate the CGH findings, fluorescence in situ hybridization analysis on 13 BA with probes specific for HER-2/neu and 20q13.2 were performed. The chromosomal alterations most often identified in BA were: gains on 8q (80%), 20q (60%), 2p, 7p and 10q (47% each), 6p (37%), 15q (33%) and 17q (30%). Losses were observed predominantly on the Y-chromosome (76%), 4q (50%), 5q and 9p (43% each), 18q (40%), 7q (33%) and 14q (30%). High-level amplifications were observed on 8q23-qter, 8p12-pter, 7p11-p14, 7q21-31, 17q11-q23. Recurrent chromosomal changes were also identified in metaplastic (gains on 8q, 6p, 10q, losses on 13q, Y, 9p) and dysplastic epithelium (gains on 8q, 20q, 2p, 10q, 15q, losses on Y, 5q, 9p, 13q, 18q). Novel amplified chromosomal regions on chromosomes 2p and 10q were detected in both Barrett's adenocarcinoma and premalignant lesions. An increase of the average number of detected chromosomal imbalances from IM (7.0 +/- 1.7), to LGD (10.8 +/- 2.2), HGD (13.4 +/- 1.1), BA (13.3 +/- 1.4), and LN (22 +/- 1.2) was seen. Although the detection of common chromosomal alterations in premalignant lesions and adjacent carcinomas suggest a process of clonal expansion, the occurrence of several chromosomal changes in an apparently random order relative to one another is striking evidence that clonal evolution is more complex than would be predicted by linear models. This is probably a reflection of the existence of many divergent neoplastic subpopulations and highlights one of the main problems associated with surveillance of Barrett's patients, namely sampling error.
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PMID:Chromosomal imbalances in Barrett's adenocarcinoma and the metaplasia-dysplasia-carcinoma sequence. 1066 85

Amplification of the Her-2/neu gene is accompanied by overexpression of its cell surface receptor product, c-erbB-2 protein. To investigate the degree of intratumoural heterogeneity we applied immunohistochemistry in primary Barrett's adenocarcinoma (BCA) (n = 6) and dysplasia adjacent to the carcinoma (n = 4). In addition, fluorescence in situ hybridisation (FISH) was performed in primary BCA (n = 5) and dysplastic areas (n = 4). For an objective evaluation digital image analysis and laser scanning microscopy were used. Five of six BCA showed a marked intratumoral heterogeneous staining pattern ranging from areas in which the tumour cells were negative or faintly positive to tumour areas with a strong staining of the entire membrane. Among the two dysplastic areas also a heterogeneous staining pattern was observed. FISH analysis revealed marked heterogeneity of intratumoral gene copy number changes in all BCA showing populations with different fractions of cells with polysomy, low level amplification and high level amplification. One dysplasia showed a minor population with Her-2/neu signal clusters. In conclusion, we observed marked intratumoural heterogeneity of c-erbB-2 protein overexpression and Her-2/neu gene copy number in the majority of the primary BCA analyzed. Digital image analysis and laser scanning microscopy were helpful in quantifying the variations in protein expression and DNA copy number in individual tumour cells. The observed heterogeneity could hamper the exact diagnostic determination of the c-erbB-2 status in small biopsies and possibly influence the effectiveness of a potential c-erbB-2 targeting therapy. Figures on http://www.esacp.org/acp/2000/20-1/walch.htm+ ++.
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PMID:Evaluation of c-erbB-2 overexpression and Her-2/neu gene copy number heterogeneity in Barrett's adenocarcinoma. 1100 35

Surveillance methods in Barrett esophagus (BE) using light microscopic examination of random biopsy specimens may miss focal dysplasia. In addition, dysplastic foci identified initially may not be relocated subsequently, making chemoprevention studies difficult. By using a special gastroscope, systematic mapping (4-quadrant biopsy specimens at 1-cm intervals) was performed in 22 patients (33 total mappings yielding 700 biopsy specimens). H&E, immunohistochemistry, and DNA ploidy analysis were performed. c-erbB-2 and positive Ki-67 were detected only in dysplastic sites; thus, their detection did not precede morphologically identifiable dysplasia. On the other hand, aneuploidy and p53 were detected in dysplastic and nondysplastic areas. p53 was correlated with dysplasia, and S-phase narrowly missed correlation, while aneuploidy was not correlated. PCNA and bcl-2 were ubiquitous, limiting their usefulness. On second maps, epithelial type was reidentified with 81% accuracy. A significant correlation was found between p53 and dysplasia. Sites of dysplasia and abnormal biomarkers could be relocated accurately by using endoscopic mapping. Therefore, mapping combined with biomarker studies may provide better surveillance and serve as a useful technique in chemoprevention studies.
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PMID:Endoscopic mapping and surrogate markers for better surveillance in Barrett esophagus. A study of 700 biopsy specimens. 1102 1


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