Abstract
BackgroundTo investigate the role of vascular endothelial growth factors (VEGF)-C/D and their receptor Flt-4 in the lymphatic metastasis of early-stage invasive cervical carcinoma.MethodsImmunohistochemical (IHC) staining with the antibodies against VEGF-C, VEGF-D, and Flt-4 was used to examine the expression of them in 97 cases of early-stage cervical carcinoma (Ia-IIa). Meanwhile, the lymphatic vessel density (LVD) was measured using the antibody against lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1). We then analyzed the correlation between Flt-4-positive vessel density (FVD), LVD and clinicopathological features of the tumors.Results(1) The positive rates of VEGF-C, VEGF-D, and Flt-4 were 57.7%, 60.8%, and 52.6% in the cervical tumor samples, respectively. (2) The expression levels of VEGF-C, VEGF-D, and Flt-4 were significantly correlated with lymphatic metastasis and lymphatic vessel invasion. LVD was significantly associated with lymph node metastasis and lymphatic vessel invasion. On the other hand, FVD was strongly associated with clinical staging. (3) The expression levels of VEGF-C and VEGF-D were significantly correlated with LVD and FVD, while Flt-4 levels showed no correlation with LVD or FVD.ConclusionVEGF-C/D and Flt-4 may play an important role in the process of lymphatic metastasis of early-stage invasive cervical carcinoma through paracrine and autocrine mechanisms.
Highlights
To investigate the role of vascular endothelial growth factors (VEGF)-C/D and their receptor Flt-4 in the lymphatic metastasis of early-stage invasive cervical carcinoma
VEGF-C/D and Flt-4 may play an important role in the process of lymphatic metastasis of early-stage invasive cervical carcinoma through paracrine and autocrine mechanisms
Expression of VEGF-C, VEGF-D and Flt-4 in cervical cancer tissue The IHC signals of VEGF-C, VEGF-D, and their receptor Flt-4 were mostly localized in the cytoplasm of the cancer cell in the examined cervical carcinoma samples and the positively stained cells showed a brown-yellow color in the cytoplasm
Summary
To investigate the role of vascular endothelial growth factors (VEGF)-C/D and their receptor Flt-4 in the lymphatic metastasis of early-stage invasive cervical carcinoma. Cervical cancer is the most common malignant gynecological cancer, and lymphatic metastasis is one of the most important metastatic routes of this cancer. Along with the development of specific markers of lymphatic endothelium [1] and the improvement of isolation techniques for lymphatic endothelial cells [2], the role of tumor lymphangiogenesis in the metastasis of early-stage cervical carcinoma is gradually becoming a research focus. The mechanism of the tumor lymphatic metastasis is still largely unknown and there is a great deal of debate over various aspects of research in the field. We employed immunohistochemical (IHC) staining to detect the expression of VEGF-C, VEGF-D, and Flt-4 in early-stage cervical carcinoma (Ia-IIa). The lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), the labeled lymphatic vessel (page number not for citation purposes)
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