Vascular endothelial growth factor (VEGF) – a valuable serum tumour marker in patients with colorectal cancer? (original) (raw)
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Elevated serum VEGF levels in colorectal cancer patients correlate with poor survival
European Journal of Cancer, 2001
Background. Vascular endothelial growth factor (VEGF) is an angiogenic cytokine involved in the progression of solid tumors. In this study we evaluated the clinical usefulness of preoperative serum VEGF concentrations in patients with colorectal cancer. The changes in serum VEGF levels after tumor surgery were also evaluated. Methods. Serum VEGF levels were determined by an enzyme-linked immunosorbent assay in the sera of 61 healthy control subjects and 67 patients with colorectal cancer preoperatively and 7 and 30 days after surgery. Results. Serum VEGF levels in patients with colorectal cancer (median, 492 pg/mL; interquartile range, 281 to 737 pg/mL) were higher (P < .0001) than in control subjects (median, 186 pg/mL; interquartile range, 100 to 273 pg/mL). There was a significant association between serum VEGF levels and disease stage, invasion depth of the tumor, the presence of lymph node and distant metastases, and the degree of differentiation. Curative but not palliative resection of the primary tumor resulted in a significant decrease of preoperative serum VEGF levels but normalized in only 72% of patients. Failure of a return of VEGF to normal after resection for cure was associated with an increased although not statistically significant risk of metastasis during follow-up. Univariate analysis showed a lower survival rate for patients with increased preoperative serum VEGF levels (P < .002). Multivariate regression analysis showed that the prognostic value of serum VEGF level was not independent of tumor stage. Conclusions. These findings suggest that VEGF plays an important role in tumor progression and the formation of distant metastases in colorectal cancer. It is at present unclear whether serial estimation of serum VEGF is clinically useful in the prediction of tumor relapse. (Surgery 2002;131:548-55.)
Annals of Oncology
Purpose: Despite plasma biomarkers offering a number of advantages over tissue-based markers, the relationship between serum vascular endothelial growth factor (VEGF) and VEGF receptor (VEGF-R) tumor expression in colorectal cancer (CRC) is still unclear. This study was designed to establish the relationship between the concentration of serum VEGF and tumor VEGF-R expression in patients with CRC. Methods: A prospective study of consecutive patients undergoing elective colorectal surgery during 1 year. Preoperative VEGF was determined by enzyme-linked immunosorbent assay and VEGF-R3 by immunochemistry. Results: The initial sample included 134 patients with CRC diagnosis. Results showed significant association of serum values of VEGF with VEGF-R3 expression (P < 0.001), even in the presence of confounders (sex, age, body mass index, tumor location, and surgical approach). The estimated effect size was high (η 2 = 0.35). Conclusion: Serum VEGF has a significant correlation with tumoral VEGF-R3 expression in CRC.
Journal of Surgical …, 2008
Background. The prognostic value of vascular endothelial growth factor (VEGF) expression in colorectal cancer is still unclear, as shown by the discordant results still reported in the literature. The aim of the study was to examine the expression of VEGF in colorectal adenocarcinomas and investigate its prognostic relevance. Materials and methods. VEGF expression was investigated by immunohistochemistry performed on tissue microarrays, in a series of 117 colorectal cancer specimens. The VEGF staining intensity in the cytoplasm of tumor cells was quantified using a semi-automated computerized image analysis and correlated with various clinicopathological characteristics and survival. Results. All tumors evaluated showed expression of VEGF, which were further divided into 49 high expression and 68 low expression tumors by their staining intensity. In tumors with lymph node metastasis, the intensity of staining of VEGF was more intense than in those without (P < 0.0001). Furthermore, the intensity of VEGF staining was more intense in Stage III tumors than those in Stage I/II (P < 0.0001). The mean number of involved lymph nodes in tumors with high VEGF staining intensity was significantly greater than in those with low staining intensity (P ؍ 0.031). Survival analysis showed a significant correlation between high levels of VEGF staining intensity and poor disease-specific survival (P < 0.0001), with independent prognostic significance in multivariate analysis (RR ؍ 3.5, P < 0.0001). In addition, patients with Stage II disease and high staining intensity of VEGF had a significantly worse disease-specific survival than those with low staining intensity (P ؍ 0.001). Conclusions. VEGF expression in colorectal cancer seems to be an independent prognostic marker of tumor behavior and may be useful to identify patients with unfavorable clinical outcome.
Surgery, 2002
Background. Vascular endothelial growth factor (VEGF) is an angiogenic cytokine involved in the progression of solid tumors. In this study we evaluated the clinical usefulness of preoperative serum VEGF concentrations in patients with colorectal cancer. The changes in serum VEGF levels after tumor surgery were also evaluated. Methods. Serum VEGF levels were determined by an enzyme-linked immunosorbent assay in the sera of 61 healthy control subjects and 67 patients with colorectal cancer preoperatively and 7 and 30 days after surgery. Results. Serum VEGF levels in patients with colorectal cancer (median, 492 pg/mL; interquartile range, 281 to 737 pg/mL) were higher (P < .0001) than in control subjects (median, 186 pg/mL; interquartile range, 100 to 273 pg/mL). There was a significant association between serum VEGF levels and disease stage, invasion depth of the tumor, the presence of lymph node and distant metastases, and the degree of differentiation. Curative but not palliative resection of the primary tumor resulted in a significant decrease of preoperative serum VEGF levels but normalized in only 72% of patients. Failure of a return of VEGF to normal after resection for cure was associated with an increased although not statistically significant risk of metastasis during follow-up. Univariate analysis showed a lower survival rate for patients with increased preoperative serum VEGF levels (P < .002). Multivariate regression analysis showed that the prognostic value of serum VEGF level was not independent of tumor stage. Conclusions. These findings suggest that VEGF plays an important role in tumor progression and the formation of distant metastases in colorectal cancer. It is at present unclear whether serial estimation of serum VEGF is clinically useful in the prediction of tumor relapse. (Surgery 2002;131:548-55.)
Association of serum vascular endothelial growth factor vegf with colorectal cancer a systemic
Vascular endothelial growth factor (VEGF) is one of the most important regulators in angiogenesis, affecting endothelial cell survival and function. Some studies have shown that serum VEGF is higher in CRC patients than in healthy control groups while other studies have given the opposite conclusion. Therefore, this meta-analysis is purposed to systemically review and evaluate the correlation between serum VEGF and CRC. Finally, 23 studies were included in this study. The meta-analysis demonstrated that serum VEGF in the cancer group was significantly higher than that in the control group (SMD: 1.5, 95% CI: 1.05-1.95, P<0.001). However, obvious heterogeneity existed among the studies (P<0.001, I2=96%) and subgroup analyses were performed to investigate the source of this heterogeneity. The results indicated that with respect to VEGF, the correlation was significant regarding tumor location, study region, age, and study size. The results of this meta-analysis showed that serum level of VEGF might be used as a candidate biomarker for CRC patients.
2015
Background: Vascular endothelial growth factor (VEGF) is a signal protein produced by cells that stimulates angiogenesis and increased vascular permeability. The prognostic value of VEGF expression in colorectal cancer is unclear as shown by the discordant results still reported in the literature. This study was designed for the evaluation of VEGF expression and correlation with clinicopathologic features in colorectal cancer. Materials and Methods: In this study, 60 paraffin – embedded blocks including colorectal cancer specimens and adjacent non-neoplastic tissues were evaluated for VEGF immunohistochemical expression and their correlation with clinicopathologic features among the patients who admitted in Sari Imam Khomeini hospital. Results: Among the 60 patients (30 males,30 females) 51.7% (31 cases) showed VEGF overexpression (High staining) , while it was 1.7% (1 case ) in adjacent normal tissue ( p =0.004). VEGF expression was correlated with stage( p -value <0.001),gr...
Cancer Growth and Metastasis, 2011
Background The aim of the present study was to determine whether serum vascular endothelial growth factor (VEGF) can provide prognostic information independent of carcinoembryonic antigen levels in patients undergoing curative surgery. Methods Serum samples were collected from 158 patients with colorectal cancer and from 100 controls. Serum and tissue levels of VEGF were measured by enzyme-linked immunosorbent assay. Serum VEGF levels in colorectal cancer patients were compared with those in healthy controls, and we retrospectively assessed the association between serum VEGF levels and clinicopathologic findings and survival. Results VEGF expression was significantly higher in colorectal cancer tissue compared with nontumor tissue. Mean serum VEGF levels in patients were significantly higher than those in controls, and significantly higher in patients with large tumors, lymph node involvement, and distant metastases. Conclusion Elevated serum VEGF was significantly associated with p...
OBJECTIVE: Determine the relationship between vascular endothelial growth factor (VEGF) expression and microvascular density (MVD) in primary colorectal cancer specimens including the prognostic value by evaluating the correlation between various common reported prognostic histopathologic indictors and these two angiogenic parameters. The Inter-observer reliability on VEGF and MVD measurement was also determined. MATERIAL AND METHOD: Anti-VEGF and anti-factor CD34 monoclonal antibodies immunohistochemical staining was performed in 40 randomly selected formalin-fixed paraffin-embedded colorectal cancer specimens of non-stage-IV patients who underwent curative resection using. Immunoreactive in 25% or more carcinoma cells was categorized as positive. The intensity of VEGF expression was graded in a semiquantitative fashion, ranging from 0 to 2 Tumor MVD was determined by counting any endothelial cells stained with CD34 per two randomly selected fields at x200 magnification in each slide. The correlation between VEGF expression and MVD was evaluated. Inter-observer agreement was assessed by comparing the results of VEGF and MVD measurements made by two pathologists. RESULTS: A moderate correlation was found between the percentage of positive immunoreactive cells and the intensity of VEGF immunoreactive staining (correlation value of 0.436, p < 0.05). MVD was found having no correlation with both the percentage of positive immunoreactive cells and intensity of VEGF immunoreactive staining (the correlation value of -0.056, p = 0.732 and 0.108, p = 0.506, respectively). Neither MVD nor VEGF expression in primary colorectal cancer tissue was found having a significant correlation with any common reported prognostic histopathologic indictors. In counting CD34-stained endothelial cells, this study revealed a high intra-observer correlation coefficient of 0.886 (95% CI: 0.715-0.955) for the first pathologist and 0.913 (95% CI: 0.782-0.965) for the second. High inter-observer reliability was found in both MVD and VEGF measurement with a substantial agreement (agreement: 95%, kappa = 0.643) between the two pathologists. CONCLUSION: In primary colorectal cancer tissues, there was no significant relationship between MVD and VEGF expression. This study revealed a high intra and inter-observer reliability on VEGF and MVD measurement. Neither MVD nor VEGF expression provided predictive value of advanced or aggressiveness of disease. Further studies on larger sample size would help validate these results.