Study of the Vascular Endothelial Growth Factor (VEGF)
Expression and Microvascular Density (MVD)
in Primary Colorectal Cancer Specimens
Sahaphol Anannamcharoen MD*,
Thirayost Nimmanon MD**
Affiliation :
* Department of Surgery, Phramongkutklao Hospital, Bangkok, Thailand
** Department of Pathology, Phramongkutklao College of Medicine, Bangkok, Thailand
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.
Keywords : Colorectal cancer, VEGF, Microvascular density, Reliability, Intra-observer, Inter-observer
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