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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TL;DR: The data indicate that the loss of the cell adhesion molecule E-cadherin in fact plays an important role in the progression of human squamous cell carcinomas, i.e., that down-regulation of expression is associated with dedifferentiation and metastasis of the tumor cells in vivo.
Abstract: Tissue sections of 32 squamous cell carcinomas (SCCs) of the head and neck were investigated for the expression of the epithelium-specific cell adhesion molecule E-cadherin. We found that E-cadherin expression is inversely correlated both with the loss of differentiation of the tumor and with lymph node metastasis. The well-differentiated SCCs expressed E-cadherin, often as strongly as the normal stratified epithelium (12 cases were tested); the moderately differentiated SCCs expressed intermediate amounts of E-cadherin or were heterogeneous (15 cases were analyzed); whereas the poorly differentiated SCCs were all E-cadherin-negative (five cases were investigated). Furthermore, seven of eight infiltrated lymph nodes of SCCs were E-cadherin-negative. These data indicate that the loss of the cell adhesion molecule E-cadherin in fact plays an important role in the progression of human squamous cell carcinomas, i.e., that down-regulation of expression is associated with dedifferentiation and metastasis of the tumor cells in vivo.
540 citations
TL;DR: Findings show that Chalkley counting is a rapid method of quantifying tumour angiogenesis and gives independent prognostic information which might be useful in diagnostic practice.
Abstract: In some studies of breast cancer, quantitation of immunohistochemically highlighted microvessel 'hot spots' has been shown to be a powerful prognostic tool. However, the antibody used, the number and size of the 'hot spots' assessed, and the stratification of patients into high and low vascular groups vary between studies. Furthermore, little is known about the relationship between microvessel density and other vascular parameters. These uncertainties and the laborious nature of the technique make it unsuitable for diagnostic practice. Both manual and computerized image analysis techniques were used in this study to examine the relationship between microvessel density and the vascular parameters in different sized microscopic fields in a pilot series of 30 invasive breast carcinomas. Automated pixel analysis of immunohistochemical staining, Chalkley point counting, and observer subjective vascular grading were also assessed as more rapid methods of measuring tumour vascularity. A Chalkley count was also performed on a further 211 invasive breast carcinomas. Significant correlations were observed between manual microvessel density and luminal perimeter (r = 0.6, P = 0.0004), luminal area (r = 0.56, P = 0.002), and microvessel number (r = 0.57, P = 0.0009) by computerized analysis. There were also significant correlations between the microscopic hot spots of 0.155 mm2 and 0.848 mm2 for microvessel number (r = 0.81, P < 0.00005), luminal perimeter (r = 0.78, P < 0.00005), and luminal area (r = 0.65, P = 0.0001). In addition, a significant correlation was observed between microvessel density and both subjective vascular grade (P = 0.002) and Chalkley count (P = 0.0001). A significant reduction in overall survival was observed between patients stratified by Chalkley count in both a univariate (P = 0.02) and a multivariate (P = 0.05) analysis in the 211 invasive breast carcinomas. These findings show that Chalkley counting is a rapid method of quantifying tumour angiogenesis and gives independent prognostic information which might be useful in diagnostic practice.
468 citations
"Prognostic impact of vascular endot..." refers background in this paper
...A number of studies have demonstrated that VEGF-A expression is associated with angiogenesis and/or has prognostic significance in solid tumors including breast (31), colorectal (32), gastric (33,34) and pancreatic cancers (35)....
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TL;DR: A large registry study provides benchmark prognostic statistics for lung cancer, and the present tumor, node, metastasis staging system well characterizes the stage-specific prognoses.
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...Although the pathologic TNM staging system has been considered to have an impact on survival in NSCLC, problems such as overlapping prognosis for patients with different tumor stages and heterogeneous prognosis for patients with the same tumor stage have been pointed out (3,7)....
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TL;DR: The data suggest that immunohistochemical receptor localization provides information complementary to standard biochemical assays in the tissues studied, and that HSCORE correlated with tumor grade for breast and endometrial carcinoma.
Abstract: A monoclonal antibody to human estrogen receptor protein (H222 Sp gamma), amplified via immunoperoxidase techniques, was used in the analysis of estrogen receptor in 452 breast carcinomas, 100 endometrial carcinomas, and 15 melanomas Immunohistochemical evaluation incorporated both intensity and distribution of staining (HSCORE) Quantitative estrogen receptor content was determined by dextran-coated charcoal analysis and sucrose density gradient analysis In all cases H222 Sp gamma localized in the nucleus of target cells A semiquantitative correlation existed between HSCORE and biochemical assays for breast and endometrial tissues The sensitivities and specificities for HSCORE as compared to the biochemical assays ranged from 80 to 95% and from 74 to 94%, respectively HSCORE correlated with tumor grade for breast and endometrial carcinoma Immunohistochemical evaluation showed no specific staining in melanomas The data suggest that immunohistochemical receptor localization provides information complementary to standard biochemical assays in the tissues studied
367 citations
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