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Abstract
Angiogenesis seems to be an early event that is associated with disease progression in cervical intraepithelial neoplasia (CIN). The aim of this study was to describe and analyze VEGF-A expression in CIN 3 and invasive cervical carcinoma, in tumor cells and stromal cells. This study comprised three groups: Group 1: 53 cases with CIN 3; Group 2: 24 cases with both CIN 3 and invasive carcinoma components; Group 3: 36 cases with invasive carcinoma. Protein expression was investigated in tumor and stromal cells by immunohistochemistry. Statistical analysis was carried out, considering the mean percentage of immunopositive cells. VEGF-A expression was higher in stromal cells in cases of invasive carcinoma (Group 3) than in CIN 3 cases (Group 1) and this difference was statistically significant. VEGF-A expression showed a borderline association between stromal cells in invasive carcinoma (Group 3) and invasive carcinoma associated with CIN 3 (Group 2). The mean percentage of cells expressing VEGF-A was significantly higher in tumor cells in CIN 3 than in stromal cells in CIN 3 (Group 1). The progression of CIN 3 to invasive carcinoma seems be determined by complex interactions between tumor and stromal cells. These findings reinforce the evidence of the role of stromal cells in tumor invasiveness.
Highlights
Cervical cancer is the third most common cancer in women worldwide and more than 85% of the global burden occurs in developing countries [1]
The mean percentage of cells expressing Vascular endothelial growth factor (VEGF)-A was significantly higher (p=0.0030) in tumor cells than in stromal cells in cases diagnosed as cervical intraepithelial neoplasia (CIN) 3 (Group 1) (Table 1)
In invasive carcinoma (Group 3), the mean percentage of cells expressing VEGF-A was higher in stromal cells than in tumor cells, but the difference was not statistically significant (p=0.0840) (Table 1)
Summary
Cervical cancer is the third most common cancer in women worldwide and more than 85% of the global burden occurs in developing countries [1]. Cervical cancer develops from a precancerous lesion referred to as cervical intraepithelial neoplasia (CIN) [2]. Invasion of cervical squamous cell carcinoma begins at the basal cell layer in a field of high-grade cervical intraepithelial neoplasia (CIN 3) [3]. Angiogenesis is the formation of neovasculature from preexisting blood vessels. It is crucial for normal body development and growth. Vascular endothelial growth factor (VEGF) is a potent mitogen responsible for the induction of angiogenesis [4,5]. The vascular endothelial growth factor (VEGF) family is comprised of highly conserved secreted glycoproteins that regulate vasculogenesis, hematopoiesis, angiogenesis, lymphangiogenesis and vascular permeability. In several types of carcinoma, including cervical cancer, a high expression of VEGF has been associated with disease progression and poor outcome [7]
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