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dcyphr | CD105 microvessels density, VEGF, EGFR-1 and c-erbB-2 and their prognostic correlation in different subtypes of cervical adenocarcinoma

Abstract

This study looks at the expression of endoglin (CD105), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR-1), and epidermal growth factor receptor 2 (c-erbB-2). The expression of these were all correlated with the prognosis of adenocarcinoma in the cervix. This study shows that cervical adenocarcinoma is caused by angiogenesis that is controlled by the interactions of CD0105, VEGF, EGFR-1, and c-erbB-2. 


Introduction

Cervical cancer has been decreasing in women overall, but cervical adenocarcinoma has been increasing in young women.  Compared to cervical carcinoma which is the most common type of cervical cancer, the cervical adenocarcinoma has a worse prognosis and does not respond as well to chemotherapy. The two subtypes of cervical adenocarcinoma are endocervical (70% of cases) and endometrioid (30% of cases). The endocervical is the most common, but the endometrioid has a worse prognosis. Cervical cancer is the most common cause of cancer death worldwide, but the subtypes and their prognosis are not well understood. Studies need to be done to see the specific microenvironment of the different types of cervical cancer so better treatment can be developed.

The growth and metastasis of a tumor depends on the density of vessels and angiogenesis. Endoglin (CD105) is involved in angiogenesis and microvascular density, which are both associated with a poor prognosis. Tumors can increase angiogenesis by secreting vascular endothelial growth factor (VEGF). VEGF is proven to promote tumor growth. Epidermal growth factor (EGFR) is also associated with poor prognosis. VEGF and EGFR are very closely related, and blocking both pathways can help treat tumors better. This study aims to look at the expression of CD105, VEGF, EGFR, and c-erbB-2 in different subtypes of cervical adenocarcinoma.


Materials and Methods

The researchers used immunohistochemistry to test the expression of VEGF, EGFR and c-erbB-2. They assessed blood microvessel density by counting all of the CD105 positive vessels per optical field under a microscope in the center and the edges of the tumor.


Results

CD105 expression and MVD assessment

In the normal tissue, CD105 expression was low. CD105 expression was highest in the endothelial cells of the center and edges of the tumor. The highest density of the tumor microvessels were at the invasion front and the stromal areas. The microvascular density varied in all of the tissue samples, but the tumor samples had a higher density on average all throughout the tissue.


VEGF expression

The VEGF reaction was found in vascular endothelial cells, fibroblasts, and inflammatory cells. The intensity of the VEGF reaction seemed to be higher when there was a higher microvascular density, independent of which subtype of cancer was looked at.


C-erbB-2 expression

The highest c-erbB-2 reactivity correlated with the highest microvascular density, independent of which subtype of cancer was looked at.


EGFR-1 expression

EGFR-1 was found in significantly lower levels than c-erbB-2.


Discussion

The expression of CD105, VEGF, EGFR-1, and c-erbB-2 and their correlation with prognosis in cervical adenocarcinoma. CD105 is known to allow normal vessels to turn into activated vessels, which are found in tumors. This study showed that the highest CD105 levels of cervical adenocarcinoma were found in the areas around the tumor. The angiogenesis of the tumor was also seen with high CD105 levels. Other studies have also shown that a higher microvascular density correlates with a worse prognosis.

 There is conflicting data from multiple studies about the use of VEGF as a prognosis predictor. Still, VEGF plays a large role in tumor angiogenesis. Some studies find that the overexpression of VEGF is linked to angiogenic tumors and the spread of cancer to the lymph nodes. But there are other studies conflicting with this link.

Most studies show EGFR to be expressed higher in squamous cell carcinoma compared to adenocarcinoma, which was supported by this study. There are mixed results on the relative expression of EGFR and c-erbB-2 in adenocarcinoma, but this study showed that c-erbB-2 was highly expressed. c-erbB-2 likely upregulates VEGF expression, which was also supposed in this study. The more we study about the microenvironment of cervical adenocarcinoma, the better we can treat this cancer.