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)

Non-small cell lung cancer is the most common cause of cancer-related death in North America and Europe. Despite improvements in the diagnosis and treatment of the disease the prognosis remains poor, the overall 5-year survival being 4-14%. An increased understanding of the molecular biology of the disease may identify novel targets for drug development. We evaluated epidermal growth factor receptor (EGFR), HER-2/neu, matrix metalloproteinase (MMP)-2, MMP-9, p53 and bcl-2 expression and microvessel density (MVD) in patients who underwent surgery with curative intent in our department between 1991 and 1996. Co-expression of EGFR/MMP-9, MVD and bcl-2 were found to be independent prognostic variables, which allowed prediction of patient outcome independent of surgical stage. Other prognostic factors identified in our series were gender, surgical stage, platelet count, extent of necrosis, the hypoxia marker carbonic anhydrase-9 and beta-catenin. In collaboration with groups in Oxford and Greece, we were also able to establish the angiogenic growth factors vascular endothelial growth factor and platelet-derived endothelial growth factor as prognostic variables. The inter-relationships between these factors are currently being examined in an expanded patient series. Through this work we hope to be able to construct an integrated biological prognostic model which can be tested in prospective studies. This work has identified several potential targets for novel therapeutic agents currently in development.
Lung Cancer 2001 Dec
PMID:Towards a biological staging model for operable non-small cell lung cancer. 1172 Jul 47

The outcomes of patients with stage I non-small-cell lung cancer (NSCLC) vary greatly, with a 5-year survival rate of approximately 60%. This study evaluated a number of molecular markers that may aid in predicting prognosis in stage I NSCLC after surgical resection. Immunohistochemical (IHC) staining of p53, HER-2/neu, bcl-2 proteins was performed on paraffin-embedded sections from 85 stage I NSCLC patients who underwent surgery and were followed up for 32 to 44 (median, 39.0; mean, 37.1) months postoperatively. Differences in survival rates were evaluated by log rank test. The prevalence of p53, HER-2/neu, and bcl-2 expression in stage I NSCLC is 59%, 29%, and 46%, respectively. HER-2/neu expression is seen more frequently in adenocarcinomas, and bcl-2 is seen more frequently in squamous carcinomas. p53 and HER-2/neu expression in stage I NSCLC is associated with significantly short survival. Patients whose tumors were both p53 and HER-2/neu positive had the worst outcome, with a survival rate of only 20%, compared with 80% in those whose tumors were both p53 and HER-2/neu negative (P = .0003). The survival rates were 54% in patients who were p53 positive but HER-2/neu negative and 50% in those who were in p53 negative, HER-2/neu positive. The differences among these 4 groups were statistically significant (P =.001). Bcl-2 does not seem to be a prognostic factor for survival. Multivariate analysis showed that overexpression of p53 and HER-2/neu, presence of angiolymphatic invasion, and tumor size > 3.0 cm were independent factors predicting poor survival. p53 and HER-2/neu by IHC staining appear to be valuable prognostic markers in stage I NSCLC patients after surgery. The worst outcome was seen in patients who expressed both p53 and HER-2/neu, suggesting that these patients might benefit from additional adjuvant therapy.
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PMID:Prognostic value of immunohistochemical expressions of p53, HER-2/neu, and bcl-2 in stage I non-small-cell lung cancer. 1182 80

HER-2/neu gene amplification and cell surface overexpression are important factors in breast cancer for prognosis and prediction of sensitivity to anti-HER-2/neu monoclonal antibody therapy. In lung cancer, the clinical significance of HER-2/neu expression is currently under evaluation. We investigated 238 non-small lung carcinomas for HER-2/neu protein overexpression by immunohistochemistry using the HercepTest. We found 2+ or 3+ overexpression in 39 patients (16%), including 35% in adenocarcinomas and 20% in large cell carcinomas, but only 1% of squamous cell carcinomas. Marked (3+) overexpression was uncommon (4%). The association between protein expression and gene copy number per cell, as determined by fluorescence in situ hybridisation assay, was investigated in 51 of these NSCLC tumours. Twenty-seven tumours (53%) were negative by both tests. Marked (3+) protein expression and gene amplification were present in only 4% of samples. In 11 tumours (21%), gene gain was accompanied by chromosomal aneusomy and did not result in high protein levels while in 7 (14%) the score 2+ was associated with maximum number of signals per cell <9. The prognostic implication of HER-2/neu protein expression was studied in 187 surgically resected tumours. No statistical difference in survival was observed comparing patients with positive (2+/3+) and negative tumours (0/1+), although 3+ patients showed a tendency to shorter survival. The therapeutic implications of protein expression and gene amplification in lung cancer need to be examined in prospective clinical trials.
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PMID:Evaluation of HER-2/neu gene amplification and protein expression in non-small cell lung carcinomas. 1198 80

Although recent advances in therapy have improved the quality of life in patients with extensive stage small cell lung cancer (ESSCLC), prolonged survival is still uncommon. To determine the role of HER-2/neu overexpression and other clinical predictors (symptoms at presentation) of adverse outcome in ESSCLC, we performed a retrospective study on subjects with a biopsy-proven diagnosis of ESSCLC. HER-2/neu overexpression was evaluated using immunohistochemistry (IHC) performed on paraffin-embedded specimens. An IHC score of > or = 2+ was considered positive for overexpression. Between 1991 and 2000, 223 patients with ESSCLC were identified, of whom 193 patients (84 females, 109 males) with a mean age of 68.5 years (range: 42-90 years) had adequate tissue specimens for HER-2/neu testing. The symptoms at initial presentation and proportionate number of patients were: weight loss 61 (31.6%), cough 53 (27.5%), dyspnea 33 (17.1%), mass on chest radiograph 18 (9.3%), chest pain 15 (7.7%), asymptomatic 14 (7.2%) and others (weakness, lymphadenopathy, hoarseness and paraneoplastic syndromes) 29 (15.0%). Of the 193 specimens, 57 (29.5%) revealed HER-2/neu overexpression. The median survival for patients with ESSCLC who were HER-2/neu positive was 8 months (range: 1-25.5 months) while that in the HER-2/neu negative group was 16 months (range: 2-34 months). Interestingly, after adjusting for age, performance status and type of therapy, subset analysis revealed that the survival was significantly lower in HER-2/neu positive individuals (P<0.001; Mann-Whitney U-test). In our study, weight loss and cough were the two most common (59%) presenting complaints in patients with ESSCLC. Also, since HER-2/neu positivity was a marker for poor prognosis in ESSCLC, testing for overexpression may play a role in identifying patients at risk for shortened survival. Further studies would delineate whether HER-2/neu overexpression renders SCLC chemoresistant and thus, adversely affects outcome. There exists a need for randomized controlled trials to assess the role of Herceptin (alone or in combination with standard chemotherapy) in patients with ESSCLC.
Lung Cancer 2002 Jun
PMID:Predictive role of HER-2/neu overexpression and clinical features at initial presentation in patients with extensive stage small cell lung carcinoma. 1200 35

We determined c-erbB-2 protein level in serum of 86 primary lung cancer patients (78 non-small cell lung carcinomas (NSCLC), 3 small cell carcinomas, 5 not histologically defined) and in 61 controls. Aim of this study was to evaluate the clinical usefulness of c-erbB-2 as marker for lung cancer diagnosis. The protein was measured with a commercially available sandwich enzyme immunoassay. Mean levels of c-erbB-2 were 72.8 +/- 122.3 fmol/ml in lung cancers and 64.6 +/- 17.5 fmol/ml in controls (P = 0.2). No association was found between c-erbB-2 levels and histotype, tumor stage, sex and smoking habits. Among NSCLC, only four patients showed a c-erbB-2 concentration higher than the selected cut-off value of 99.6 fmol/ml. Subjects with levels higher than the 75th percentile in tumors (73 fmol/ml) had a shorter median survival than those with lower levels (6.3 months versus 10.0 months, P = 0.003). Our results indicated that serum c-erbB-2 protein is not a reliable diagnostic marker. There is, however, a suggestion of a possible clinical usefulness in terms of survival prediction.
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PMID:c-erbB-2 protein in serum of primary lung cancer patients. 1208 5

It has been suggested that uPA in cancer cells is up regulated by the p 185 kD form of the HER-2/neu oncogene. We elected to see if the extra cellular domain of HER-2/neu, the p 105 fraction, which is found in the circulation, has any regulatory influence on uPA or uPAR in those patients with NSCLC Levels of uPA, uPAR and p 105 HER-2/neu were determined in blood from age-matched controls and patients with advanced NSCLC. In the patients with NSCLC, samples were obtained before and following treatment. A large increase in both uPA and uPAR compared to controls was seen in the patients prior to treatment. The uPAR level post-treatment decreased from pre-treatment values, which is favorable. There was a significant increase in uPA and a decrease in HER-2/neu in the post-treatment time frame. Additionally, correlation analysis of circulating uPAR, uPA and HER-2/neu against each other in both the controls and treatment groups indicated no relationship. It appears that circulating uPA and uPAR are elevated in NSCLC patients. The up-regulation of uPA by HER-2/neu seen in lung cancer cells in vitro is apparently lost in the blood in vivo as is evidenced by the lack of correlation between them which is also true for the receptor as well.
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PMID:The circulating urokinase plasminogen activator (uPA) and its soluble receptor (suPAR) are not up-regulated by the circulating P105 fraction of the HER-2/neu proto-oncogene: in vivo evidence from patients with advanced non-small cell lung cancer (NSCLC). 1217 85

Overexpression of receptor-type tyrosine kinases in various cancers is associated with an aggressive tumor phenotype and poor outcome, but their expression had never been evaluated in large cell neuroendocrine carcinoma (LCNEC) of the lung. In the present study, we investigated the expression of three receptor tyrosine kinases, epidermal growth factor receptor (EGFR), c-erbB-2, and c-kit protein, by comparing surgically resected 40 LCNECs with other neuroendocrine (NE) lung tumors: 9 typical carcinoids (TCs), 5 atypical carcinoids (ACs), and 13 small cell lung carcinomas (SCLCs). None of the NE lung tumors showed expression of EFGR or c-erbB-2, but c-kit was overexpressed in 55% of the LCNEC tumor cells and 46% of the SCLC tumor cells. None of the clinicopathologic factors in either the LCNEC or SCLC patients correlated with c-kit overexpression. The finding that c-kit expression in LCNEC is similar to its expression in SCLC suggests that inhibition of c-kit may be effective as a therapy targeting LCNEC as well as SCLC.
Lung Cancer 2003 May
PMID:Frequent overexpression of the c-kit protein in large cell neuroendocrine carcinoma of the lung. 1271 Nov 18

C-erbB-2 prognostic value for survival in patients with lung cancer remains controversial. We performed a systematic review of the literature to clarify its impact. Studies were identified by an electronic search in order to aggregate the survival results, after a methodological assessment using the scale of the European Lung Cancer Working Party. To be eligible, a study had to deal with c-erbB-2 assessment in lung cancer patients and to analyse survival according to c-erbB-2 expression. In total, 30 studies were eligible: 24 studies dealt with non-small-cell lung carcinoma (NSCLC), five with adenocarcinoma and one study dealt with small-cell carcinoma. In all, 31% of the patients were positive for c-erbB-2. According to c-erbB-2 expression, 13 studies were 'negative' (significant detrimental effect on survival), one 'positive' (significant survival improvement) and 16 not significant. Significant studies had a better subscore relative to analysis and results report than nonsignificant studies. In total, 86% of the significant studies and only 56% of the nonsignificant studies were evaluable for the meta-analysis. This suggests a possible bias in our aggregated results. For NSCLC, the hazard ratio was 1.55 (95% CI: 1.29-1.86) in favour of tumours that do not express c-erbB-2. In conclusion, the overexpression of c-erbB-2 might be a factor of poor prognosis for survival in NSCLC, but there is a potential bias in favour of the significant studies with an overestimation risk of the magnitude of the true effect of c-erbB-2 overexpression.
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PMID:The role of HER-2/neu expression on the survival of patients with lung cancer: a systematic review of the literature. 1296 8

HER-2/ neu is an immunogenic protein eliciting both humoral and cellular immune responses in patients with HER-2/ neu-positive ((+)) tumors. Preexisting cytotoxic T lymphocyte (CTL) immunity to HER-2/ neu has so far been mainly evaluated in terms of detection of CTL precursor (CTLp) frequencies to the immunogenic HLA-A2-binding nona-peptide 369-377 (HER-2(9(369))). In the present study, we examined patients with HER-2/ neu(+) breast, ovarian, lung, colorectal, and prostate cancers for preexisting CTL immunity to four recently described HER-2/ neu-derived and HLA-A2-restricted "cytotoxic" peptides and to a novel one spanning amino acids 777-785 also with HLA-A2-binding motif. We utilized enzyme-linked immunosorbent spot (ELISpot) assay, which allows a quantitative and functional assessment of T cells directed against specific peptides after only brief in vitro incubation. CTL reactivity was determined with an interferon gamma (IFN-gamma) ELISpot assay detecting T cells at the single cell level secreting IFN-gamma. CTLp were defined as peptide-specific precursors per 10(6) peripheral blood mononuclear cells (PBMCs). Patients' PBMCs with increased CTLp were also tested against autologous tumor targets and peptide-pulsed dendritic cells (DCs) in cytotoxicity assays. We also studied patients with HER-2/ neu-negative ((-)) tumors and healthy individuals. Of the HER-2/neu(+) patients examined, 31% had increased CTLp to HER-2(9(952)), 19% to HER-2(9(665)), 16% to HER-2(9(689)), and 12.5% HER-2(9(435)), whereas only 2 of 32 patients (6%) responded to HER-2(9(777)). The CTLp recognizing HER-2(9(952)) were extremely high in two patients with breast cancer, one with lung cancer, and one with prostate cancer. None of the HER-2/neu(-) patients or healthy donors exhibited increased CTLp to any of these peptides. Besides IFN-gamma production, preexisting CTL immunity to all five HER-2/ neu peptides was also shown in cytotoxicity assays where patients' PBMCs with increased CTLp specifically lysed autologous tumor targets and autologous peptide-pulsed DCs. Our results demonstrate for the first time that (1) preexisting immunity to peptides HER-2(9(435)), HER-2(9(952)), HER-2(9(689)), HER-2(9(665)), and HER-2(9(777)) is present in patients with HER-2/ neu(+) tumors of distinct histology, (2) HER-2(9(777)) is a naturally processed peptide expressed on the surface of HER-2/ neu(+) tumors, as are the other four peptides, and (3) HER-2/ neu(+) prostate tumor cells can be recognized and lysed by autologous HER-2 peptide-specific CTL. Our findings broaden the potential application of HER-2/ neu-based immunotherapy.
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PMID:Natural CD8+ T-cell responses against MHC class I epitopes of the HER-2/ neu oncoprotein in patients with epithelial tumors. 1368 Jan 93

The prognostic value of p53 and c-erbB-2 immunostaining and preoperative serum levels of CEA and CA125 was investigated in a prospective multicentric study including 465 consecutive non-small cell lung cancer (NSCLC) patients with resectable tumors. Four end-points were used: lung cancer death, first relapse (either locoregional or metastasis), loco-regional recurrence and metastasis development. Standard statistical survival methods (Kaplan-Meier and Cox regression) were used. The specificity of the prognostic effect across different types of tumors was also explored, as had been planned in advance. Our results showed, once again, that pathological T and N classifications continue to be the strongest predictors regarding either relapse or mortality. Three of the studied markers seemed to add further useful information, however, but in a more specific context. For example, increased CEA concentration defined a higher risk population among adenocarcinomas but not among people with squamous tumors; and p53 overexpression implied a worse prognosis mainly in patients with well differentiated tumors. The analysis of type of relapse proved to be very informative. Thus, CA125 level was associated with a worse prognosis mainly related with metastasis development. Another interesting result was the influence of smoking, which showed a clear dose-response relationship with the probability of metastasis. For future studies, we recommend the inclusion of different endpoints, namely considering the relationship of markers with the type of relapse involved in lung-cancer recurrence. They can add useful information regarding the complex nature of prognosis.
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PMID:Clinical value of p53, c-erbB-2, CEA and CA125 regarding relapse, metastasis and death in resectable non-small cell lung cancer. 1456 28


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