Prognostic impact of vascular endothelial growth factor-A and E-cadherin expression in completely resected pathologic stage I non-small cell lung cancer.
01 Jul 2010-Japanese Journal of Clinical Oncology (Oxford University Press)-Vol. 40, Iss: 7, pp 670-676
TL;DR: Gender, vascular endothelial growth factor-A and E-cadherin expression were significant predictive factors for overall survival in completely resected pathologic stage I non-small cell lung cancer.
Abstract: OBJECTIVE: The purpose of this study was to evaluate the value of vascular endothelial growth factor-A and E-cadherin expression as well as other confirmed prognostic factors in predicting the clinical outcome after definitive surgery of pathologic stage I non-small cell lung cancer. METHODS: One hundred and eighty-five consecutive and non-selected patients who underwent definitive surgery for stage I non-small cell lung cancer in our institute were included in this study. Formalin-fixed paraffin-embedded specimens were stained for vascular endothelial growth factor-A and E-cadherin and the correlation between the staining, its clinicopathological parameters and its prognostic power were analyzed statistically. RESULTS: Of the 185 patients studied, 92 cases (49.7%) were strongly positive for vascular endothelial growth factor-A. Vascular endothelial growth factor-A expression was only related to visceral pleural involvement (P < 0.001). A total of 95 carcinomas (51.4%) were E-cadherin-negative tumors. E-cadherin expression correlated with histology (P < 0.001), tumor size (P = 0.001) and visceral pleural involvement (P < 0.001). In univariate analysis by log-rank test, gender, tumor size, lymphovascular invasion, visceral pleural involvement, vascular endothelial growth factor-A expression and E-cadherin expression were significant prognostic factors (P = 0.003, 0.042, 0.026, 0.035, 0.008 and 0.006, respectively). In multivariate analysis, gender, vascular endothelial growth factor-A and E-cadherin expression maintained its independent prognostic influence on overall survival (P = 0.013, <0.001 and 0.036, respectively). CONCLUSIONS: Expression of vascular endothelial growth factor-A is related to visceral pleural involvement, and E-cadherin expression correlates with histology, tumor size and visceral pleural involvement. Multivariate analysis confirmed gender, vascular endothelial growth factor-A and E-cadherin expression were significant predictive factors for overall survival in completely resected pathologic stage I non-small cell lung cancer.
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TL;DR: In this paper, the authors performed a systematic review and meta-analysis to evaluate whether the presence of lymphovascular invasion (LVI) is associated with disease outcome in stage I NSCLC patients.
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TL;DR: This study analyzed the soluble factors secreted by lung tumor-associated osteoblast (TAOB), which are responsible for increasing cancer progression, to provide novel evidence that inhibition of B MP-2 or BMP-2-mediated MAPK/Runx2/Snail signaling is an attractive therapeutic target for osteolytic bone metastases in lung cancer patients.
68 citations
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 background or methods from "Prognostic impact of vascular endot..."
...In these six studies with 717 patients [16,17,19,23,25,26], the combined HR was 1....
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...E-cadherin expression and clinicopathological parameters in patients with NSCLC The following clinicopathological parameters extracted from studies were collected for analysis: histological type [16,17,19,20,29,31,33,35,38–41], grade of differentiation [14– 20,25,31,35,37–39], tumor size [14,15,17,19,35,38], lymph node metastasis [14–17,19,29,31,35,38,41], pleural invasion [16,26,38], vascular invasion [14,16], and TNM stages [16,17,19,20,29,31, 33,35,38–41]....
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TL;DR: Gender differences in terms of risk factors, histopathological features and pathogenetic mechanisms in NSCLC are summarized, and it is hypothesized that a gender-oriented pharmacology could beneficially impact on innovative therapeutic strategies.
38 citations
Cites background from "Prognostic impact of vascular endot..."
...The possible implication of gender-associated risk factors or autoantibodies in modifying tumor microenvironment, including vascular integrity and function, has been instead recently investigated [42,75–77]....
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TL;DR: Exposure to decreased E-cadherin expression was associated with poor survival in patients with NSCLC, especially among Asians, but was not significantly correlated with survival for stage INSCLC patients.
Abstract: E-cadherin has been implicated in invasiveness and metastasis. However, the clinical prognostic value of decreased E-cadherin expression in patients with non-small cell lung cancer (NSCLC) remains unsettled. A meta-analysis of eligible studies was performed to quantitatively review the correlation of decreased E-cadherin expression with survival in patients with NSCLC. Thirteen studies, including 2,274 patients, were subjected to final analysis. The rate of decreased E-cadherin expression was 47.6 % overall and 41.4 % for stage I disease. The combined hazard ratio (HR) was 1.41 (95 % CI 0.18-1.65; P = 0.001), indicating that decreased E-cadherin expression had an unfavorable impact on the survival of patients with NSCLC. Further, in the stratified analysis by ethnicity, the combined HR in Asians was 1.49 (95 % CI 1.27-1.71) and in non-Asians was 1.01 (95 % CI 1.00-1.02). However, when only the stage I studies were considered, the combined HR was 1.19 (95 % CI 0.90-1.47; P = 0.576), suggesting that decreased E-cadherin expression has no impact on survival. Decreased E-cadherin expression was associated with poor survival in patients with NSCLC, especially among Asians, but was not significantly correlated with survival for stage I NSCLC patients.
35 citations
Cites background from "Prognostic impact of vascular endot..."
...Two studies created continuous scores for E-cadherin expression [18, 19] with the remaining studies dichotomizing E-cadherin expression according to the proportion of the tissue staining positive for E-cadherin....
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References
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TL;DR: Univariate analysis revealed tumour size, nodal status, microvessel density and VEGF and PD-ECGF expression as significant prognostic factors and underlines the prognostic significance of microvessels density in operable NSCLC.
Abstract: High microvessel density, an indirect measure of angiogenesis, has been shown to correlate with increased tumour size, lymph node involvement and poor prognosis in non-small-cell lung cancer (NSCLC). Tumour cell vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) expression correlate with angiogenesis and a poor outcome in this disease. In a retrospective study VEGF and PD-ECGF expression and microvessel density were evaluated immunohistochemically in surgically resected specimens (T1-3, N0-2) from 223 patients with operable NSCLC using the VG1, P-GF.44C and JC70 monoclonal antibodies respectively. High VEGF immunoreactivity was seen in 104 (46.6%) and PD-ECGF in 72 (32.3%) cases and both were associated with high vascular grade tumours (P= 0.009 and P= 0.05 respectively). Linear regression analysis revealed a weak positive correlation between VEGF and PD-ECGF expression in cancer cells (r= 0.21; P = 0.002). Co-expression of VEGF and PD-ECGF was not associated with a higher microvessel density than VEGF or PD-ECGF only expressing tumours. Furthermore a proportion of high vascular grade tumours expressed neither growth factor. Univariate analysis revealed tumour size, nodal status, microvessel density and VEGF and PD-ECGF expression as significant prognostic factors. Tumour size (P < 0.02) and microvessel density (P < 0.04) remained significant on multivariate analysis. In conclusion, VEGF and PD-ECGF are important angiogenic growth factors and have prognostic significance in NSCLC. Furthermore the study underlines the prognostic significance of microvessel density in operable NSCLC.
281 citations
Journal Article•
TL;DR: Reduction of α-cat expression is more correlated with invasive phenotype and lymph node metastasis than E-cad expression in human esophageal cancer and that α-Catenin is also involved in invasion and metastasis.
Abstract: Intercellular adhesion of the epithelial tissue is mainly regulated by the E-cadherin (E-cad) molecule. α-Catenin (α-cat) is one of the E-cad-associated cytoplasmic proteins that forms a linkage to the cytoskeleton and regulates E-cad function. To investigate the mechanism of dysfunction in cell-cell adhesion in cancerous tissues, we examined E-cad and α-cat expression by immunohistochemical staining on 46 human esophageal cancers using our specific monoclonal antibodies. By grading of E-cad and α-cat expression as uniformly positive (+), heterogeneous (±), or uniformly negative (−), the 46 tumors could be classified into 9 (20%) E-cad(+)/α-cat(+), 15 (33%) E-cad(±)/α-cat(±), 21 (46%) E-cad(±)/α-cat(−), and 1 (2%) E-cad(−)/α-cat(−). Twenty-five (54%) of the 46 tumors showed a similar expression of both molecules, while the other 21 tumors (46%) showed E-cad(±)/α-cat(−). Thus, although the expression of α-cat was significantly correlated with that of E-cad, in some tumors the reduction of α-cat was greater. Regarding the clinicopathological features, the reduction of α-cat expression, as well as that of E-cad, was significantly associated with tumor dedifferentiation, infiltrative growth, and lymph node metastasis (P These results suggest that not only E-cad but also α-cat are important regulators of intercellular adhesion and that α-cat is also involved in invasion and metastasis. In particular, reduction of α-cat expression is more correlated with invasive phenotype and lymph node metastasis than E-cad expression in human esophageal cancer. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
256 citations
Journal Article•
TL;DR: The results show the suppressive effects of E-cadherin expression on bone metastasis by circulating breast cancer cells and suggest that the modulation of expression of this CAM may reduce the destructive effects of Breast cancer cells on bone.
Abstract: The molecular mechanisms by which human cancer cells spread to bone are largely unexplored. The process likely involves cell adhesion molecules (CAMs) that are responsible for homophilic and heterophilic cell-cell interactions. One relevant CAM may be the calcium-dependent transmembrane glycoprotein E-cadherin. To investigate the involvement of E-cadherin in breast cancer metastasis to bone, we used an in vivo model in which osteolytic bone metastases preferentially occur after injections of cancer cells directly into the arterial circulation through the left ventricle of the hearts of nude mice. We have found that E-cadherinnegative human breast cancer cells MDA-MB-231 (MDA-231) develop radiographically detectable multiple osteolytic bone metastases and cachexia in this model. However, MDA-231 breast cancer cells that were transfected with E-cadherin cDNA showed a dramatically impaired capacity to form osteolytic metastases and induce cachexia. Histological and histomorphometrical analyses of bones of mice bearing mock-transfected MDA-231 revealed aggressive metastatic tumor, whereas metastatic tumor burden was significantly decreased in the bones of mice bearing E-cadherin-expressing MDA-231. Nude mice bearing E-cadherin-transfected MDA-231 breast cancer cells survived longer than mice bearing mock-transfected MDA-231 breast cancer cells. Anchorage-dependent and -independent growth in culture and tumor enlargement in the mammary fat pad of nude mice were unchanged between mock-transfected and E-cadherin-expressing MDA-231, suggesting that these differences in metastatic behavior are not due to an impairment of cell growth and tumorigenicity. Our results show the suppressive effects of E-cadherin expression on bone metastasis by circulating breast cancer cells and suggest that the modulation of expression of this CAM may reduce the destructive effects of breast cancer cells on bone.
193 citations
"Prognostic impact of vascular endot..." refers background in this paper
...E-cadherin is one of the metastatic suppressor genes (11,17)....
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TL;DR: Emerging evidence indicates that there are differences in the pathogenesis and possibly increased susceptibility to lung cancer in women and considerable data support small, but important differences favoring women in terms of response to therapy and long-term survival after the diagnosis of lung cancer, regardless of histology or stage.
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...Exogenous or endogenous estrogens (48), gene and emotional factors may also play important roles in the development and survival of the lung cancer for women (49)....
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TL;DR: The expression of vascular endothelial growth factor was one of the most important prognostic factors in completely resected non-small-cell lung cancer, especially in squamous cell carcinoma.
167 citations
"Prognostic impact of vascular endot..." refers background in this paper
...Owing to developments in molecular biology, many clinical studies on molecular markers associated with tumor biological behavior have been performed in human cancers, and these molecular markers, including oncogenes, tumor suppressor genes (10), metastatic suppressor genes (11) and angiogenetic factors (12,13), could be prognostic factors for NSCLC patients....
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