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Journal ArticleDOI

Prognostic Value of Epithelial Growth Factor Receptor, Vascular Endothelial Growth Factor, E-Cadherin, and p120 Catenin in Resected Non-Small Cell Lung Carcinoma

01 Aug 2011-Archivos De Bronconeumologia (Arch Bronconeumol)-Vol. 47, Iss: 8, pp 397-402
TL;DR: While negativeStaining of EGFR was related with poor survival, staining of VEGF, E-cadherin, and p120 catenin were not related with survival in patients with resected NSCLC.
Abstract: Introduction Several markers have been investigated to predict the prognosis of lung cancer. In the present study, the prognostic values of epithelial growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), E-cadherin, and p120 catenin expression were investigated by immunohistochemistry in patients with a surgically resected non-small cell lung carcinoma (NSCLC). Patients and method EGFR, VEGF, E-cadherin, and p120 catenin expression were prospectively determined in resected specimens from patients with NSCLC who had undergone surgery between 2003 and 2007. Patients’ and disease-related general characteristics and survival rate were recorded. Results One hundred seventeen patients with a mean age of 61.3 years were included in the study. After a mean follow-up of 27.5 months, the median survival was determined to be 44.0 months and the 5-year survival was 46.2%. The 5-year survival in negative and positive staining groups were as follows; 32% and 66.7% for EGFR (P=.02), 37.8%, and 50.7% for VEGF (P=.5), 41% and 66% for E-cadherin (P=.19), and 46% and 50% for p120 catenin (P=.27). The differentiation, N status, stage, and EGFR staining were variables significantly affecting survival (P=.001, .006, .03, and .02, respectively). In multivariate Cox analysis, the EGFR staining level and N status were variables those significantly affecting survival (P=.021 and P=.010). Conclusions While negative staining of EGFR was related with poor survival, staining of VEGF, E-cadherin, and p120 catenin were not related with survival in patients with resected NSCLC.
Citations
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Journal ArticleDOI
TL;DR: Levels of CD133, CD44, and ALDH1 had independent prognostic value to predict the recurrence of lung adenocarcinoma, and showed a significantly higher risk of recurrence than the corresponding low expressers.
Abstract: The present study investigated expression profiles of the potential CSC markers including CD133, CD44, ALDH1, and β-catenin, and evaluated their prognostic value in lung adenocarcinomas. One-hundred-and-seventy-seven tumors (stage I) were immunohistochemically examined for the expression of these markers, and thresholds to subdivide expression levels were determined using receiver operating characteristics curves. Tumors with high levels of CD133 (adjusted hazard ratio (HR) 4.55 (95% confidence interval (CI) 1.26-16.40, P = 0.021), CD44 (HR 3.73, 95% CI 1.20-11.58, P = 0.023) or ALDH1 (HR 3.61, 95% CI 1.09-12.3, P = 0.036), but not β-catenin (HR 2.43, 95% CI 0.59-10.8, P = 0.220), showed a significantly higher risk of recurrence than the corresponding low expressers. In conclusion, levels of CD133, CD44, and ALDH1 had independent prognostic value to predict the recurrence of lung adenocarcinoma.

86 citations

Journal ArticleDOI
TL;DR: Regardless of the presence of an underlying respiratory condition (COPD), protein oxidation, oxidatively damaged DNA, and inflammation were remarkably increased in the normal airways and blood of patients with LC.

74 citations


Cites background from "Prognostic Value of Epithelial Grow..."

  • ...Importantly, interferon-γ, TGF-β, and VEGF levels were also greater in the blood, but not in the normal epithelium, of patients with only COPD than in non-COPD controls....

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  • ...Systemic levels of TGF-β and VEGF were significantly greater in LC-COPD, LC, and COPD patients compared to non-COPD controls (Figs....

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  • ...All LC patients showed a significant rise in VEGF levels compared to control subjects, both COPD and non-COPD (Fig....

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  • ...Moreover, genetic variations of TGF-β [46] and systemic levels of TNF-α [47] and VEGF [48] were also shown to have potential implications in the survival of LC patients undergoing therapy....

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  • ...In the current investigation, levels of the cytokines TNF-α, interferon-γ, TGF-β, and VEGF were greater in the normal bronchi of all patients with LC than in non-COPD controls....

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Journal ArticleDOI
TL;DR: Forkhead box M1 may be used as a prognostic indicator for patients with NSCLC and promotes metastasis by inducing EMT of lung cancer cells through activation of the AKT/p70S6K pathway.
Abstract: Forkhead box M1 (FOXM1), a member of the Fox family of transcriptional factors, is considered to be an independent predictor of poor survival in many solid cancers. However, the underlying mechanism is not yet clear. The aim of the present study was to investigate the clinical significance of the correlation between FOXM1 and epithelial-mesenchymal transition (EMT) in non-small cell lung carcinoma and the possible mechanism responsible for FOXM1-induced EMT and metastasis. In the present study, expression levels of FOXM1 and EMT indicator proteins were determined by tissue microarray (TMA) and immunohistochemical staining, western blotting and reverse transcription-PCR (RT-PCR). Other cellular and molecular approaches including gene transfection, small interfering RNA (siRNA), and migration and invasion assays were utilized. Our results demonstrated that FOXM1 overexpression was statistically significantly associated with a higher TNM stage (p=0.036), lymph node metastasis (p=0.009) and a positive smoking history of the patients (p=0.044). Additionally, high expression of FOXM1 correlated with loss of E-cadherin expression (p<0.001) and anomalous immunopositivity of Vimentin (p=0.002). Moreover, patient survival analysis demonstrated that high expression of FOXM1 (p=0.043) and the presence of lymph node metastasis (p=0.042) were independent prognostic factors for non-small cell lung cancer (NSCLC). Furthermore, various in vitro experiments indicated that overexpression or knockdown of FOXM1 expression altered EMT through activation or inhibition of the AKT/p70S6K signaling pathway. Collectively, the results suggest that FOXM1 may be used as a prognostic indicator for patients with NSCLC and promotes metastasis by inducing EMT of lung cancer cells through activation of the AKT/p70S6K pathway. Therefore, we suggest that FOXM1 may be a potential target for lung cancer therapy.

64 citations

Journal ArticleDOI
30 Jun 2014-PLOS ONE
TL;DR: Downregulated E-cadherin expression detected by IHC seems to correlate with tumour progression and could serve as an important prognostic factor in patients with NSCLC.
Abstract: BACKGROUND Many studies have investigated the prognostic role of E-cadherin in patients with NSCLC; however, the result still remains inconclusive. An up-to data system review and meta-analysis was necessary to give a comprehensive evaluation of prognostic role of E-cadherin in NSCLC. METHODS Eligible studies were searched in Pubmed, Embase and Web of Science databases. The inclusion criteria were studies that assessed the relationship between E-cadherin expression detected by immunohistochemistry (IHC) and the prognosis or clinicopathological features in patients with NSCLC. Subgroup analysis according to race, percentage of reduced/negative E-cadherin expression, histological type, and sample size were also conducted. Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were calculated to examine the risk or hazard association. RESULTS A total of 29 studies including 4010 patients were qualified for analysis. The analysis suggested that downregulated E-cadherin expression was significant associated with unfavorable overall survival (OS) and disease-free survival/progression-free survival (DFS/PFS) in patients with NSCLC. Subgroup analysis by race, percentage of reduced/negative E-cadherin expression, sample size also found the significant association in OS. When only the stage I NSCLC were considered, downregulated E-cadherin expression still had an unfavorable impact on OS. Additionally, downregulated E-cadherin expression was significantly associated with differentiation grade, lymphnode metastasis, vascular invasion, and TNM stage. CONCLUSION Downregulated E-cadherin expression detected by IHC seems to correlate with tumour progression and could serve as an important prognostic factor in patients with NSCLC.

47 citations


Cites result from "Prognostic Value of Epithelial Grow..."

  • ...Among these 22 studies, 17 studies evaluated patients in Asian [14–17,19,20,23,25,26,29,31–36], five studies evaluated patients in Caucasian [18,21,27,28,30]....

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  • ...Further subgroup analysis by race suggested that both Asian and Caucasian patients with reduced E-cadherin had a significant impact on OS (Asian: HR = 1.67, 95% CI = 1.42–1.96, p,0.001, I2 = 41.5%, P = 0.038; Caucasian: HR = 1.37, 95% CI = 1.12– 1.66, p = 0.002, I2 = 0.0%, P = 0.592)....

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Journal ArticleDOI
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TL;DR: Analysis of a collected database representing all clinical, surgical-pathologic, and follow-up information for 5,319 patients treated for primary lung cancer confirmed the validity of the TNM and stage grouping classification schema.

4,526 citations

Journal ArticleDOI
TL;DR: EGFR overexpression is frequent in NSCLC, is most prominent in SCC, and correlates with increased gene copy number per cell, and high gene copy numbers per cell showed a trend toward poor prognosis.
Abstract: Purpose: The epidermal growth factor receptor (EGFR) is frequently overexpressed in non–small-cell lung carcinoma (NSCLC), and EGFR inhibitors are promising new therapeutic agents. The molecular mechanisms responsible for EGFR overexpression are poorly understood. Materials and Methods: Gene copy number and protein status of EGFR were investigated in microarrayed tumors from 183 NSCLC patients, including squamous cell carcinoma (SCC; 89 patients) and non-SCC (94 patients) histologies. Protein expression was assessed by immunohistochemistry on a scale from 0 to 400 (percentage of positive cells × staining intensity). Gene and chromosome 7 copy numbers were identified by fluorescent in situ hybridization (FISH). Results: EGFR protein overexpression was observed in 62% of the NSCLC (25% scored 201 to 300; 37% scored 301 to 400), more frequently in SCC than non-SCC (82% v 44%; P < .001), and in 80% of the bronchioloalveolar carcinomas. The prevalent FISH patterns were balanced disomy (40%) and trisomy (38%) f...

1,408 citations

Journal ArticleDOI
TL;DR: General thoracic surgery , General thorACic surgery, کتابخانه دیجیتالی دانشگاه علوم پزشدکی و شهید بهشتی.
Abstract: This second edition consists of 18 sections with 75 chapters written by 79 contributors. Of these, 26 chapters are new, reflecting advances in thoracic surgery during the past ten years. Diaphragmatic pacing, lung transplantation, and laser endoscopic procedures are examples of this expanding field. The text is arranged in a logical sequence of anatomy, physiology, diagnostic procedures, and preoperative evaluation. Following is more specific consideration of the surgical treatment of trauma and diseases of the chest wall, diaphragm, lungs, esophagus, and mediastinum. The section on anesthetic treatment of patients undergoing thoracic surgery includes discussion of postoperative care and ventilatory support. Considerable attention is devoted to the continuing study of the function and motor disturbances of the esophagus in the sections on physiology and the esophagus. Chapters dealing with radiation therapy, chemotherapy, and immunology discuss the optional or adjuvant therapies currently available. Technical aspects are well presented in the section on

1,025 citations

Journal Article
TL;DR: The association between overexpression of EGFR, TGF-alpha, or both, and overall survival of patients with resectable NSCLC, and findings suggest that this growth factor/receptor loop is more important for lung tumor formation than for tumor progression.
Abstract: The epidermal growth factor receptor (EGFR) and its ligand transforming growth factor (TGF) alpha are hypothesized to form an autocrine growth loop in non-small cell lung cancer (NSCLC) and to play an important role in tumor formation and progression We studied the association between overexpression of EGFR, TGF-alpha, or both, and overall survival of patients with resectable NSCLC Overexpression, defined as >20% of tumor cells staining on immunohistochemistry, was examined in 96 tumor samples from consecutive patients having resection of previously untreated, well-staged NSCLC who were then followed prospectively (median follow-up, 207 months) The expression of three other ligands for EGFR (epidermal growth factor, cripto, and amphiregulin) was examined by Northern analysis to determine whether they might also contribute to a potential growth stimulatory loop Overall, survival was calculated by the method of Kaplan and Meier, and prognostic factors were compared using the log-rank test Overexpression of EGFR only was found in 32% (31 of 96), of TGF-alpha only in 10% (10 of 96), of both EGFR and TGF-alpha in 38% (37 of 96), and of neither in 19% (19 of 96) of tumors EGFR and TGF-alpha overexpression was observed in all tumor stages and histological types but was most frequent in squamous cell carcinoma By univariate and multivariate analyses, only tumor stage, not histology or overexpression of EGFR, TGF-alpha, or both, had a significant impact on overall survival No expression of epidermal growth factor or cripto was observed at the total cellular RNA level of Northern analysis in tumor or benign lung, suggesting that in NSCLC these ligands may not participate in an autocrine growth stimulatory loop with EGFR Differential overexpression of amphiregulin in malignant versus normal lung was observed, but this expression pattern did not have a prognostic impact Thus, EGFR and TGF-alpha overexpression is frequent in early-stage NSCLC but is not associated with a survival difference These findings suggest that this growth factor/receptor loop is more important for lung tumor formation than for tumor progression

425 citations

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