Vascular Endothelial Growth Factor (VEGF-C) Protein Expression Related with Lymphangiogensis in Iraqi Cervical Cancer Patients

Abstract

Objective: Metastatic spread of tumor cells to distant organs is the leading cause of mortality from cancer. Although metastatic tumor spread can occur via a different mechanism. lymphangiogenic factors recognized were vascular endothelial growth factor (VEGF)–C and –D, which bind to a tyrosine kinase receptor, VEGF receptor (R)–3. Binding affinities to VEGFR-2 receptor increase on the lymphatic and blood endothelium therefore enables both growth factors to also exert lymphangiogenic and angiogenic effects and increased incidence of lymph node metastasis. The aim of this study is to evaluate the VEGF-C protein expression in cervical cancer cells and lymph vessels and found the relationship of this marker with lymphangiogensis of Iraqi cervical cancer samples. Method: In this study, expression of VEGF-C was noticed in 55 cervical samples by Immuno- histochemistry. 35 cases diagnosed as invasive cervical cancer in addition to 20 normal samples consider as control. Immunohistochemistry was performed and the cytoplasm level of VEGF-C was scored by the percentage of positive cells and intensity. Results: The present data evaluated the prognostic significance of VEGF-C to cervical cancer, cytoplasm staining was seen in 29 cases (82.9 %) in cervical cancer tissues. Only 4 out of 35 cases (11.4 %) displayed cytoplasmic and nuclear tissue. There is significant difference of VEGF-C staining in lymphatic vessels and cancer cells (χ2= 5.04, p = 0.023*) regarding to positive expression (20/ 57.1%), (25/ 71.4 %) respectively and negative VEGF-C staining 15 (42.9%), 10 (28.6 %) respectively. High positive percentage of VEGF-C expression in cytoplasm of malignant cases in score 2& 3 (25.7%, 45.7 %, P-value= 0.0392 *, 0.029* respectively) as compared to normal cases (15%, 30% respectively). Demographic criteria of patients revealed association with VEGF-C expression patterns. Differentiation Well + moderately and histologic type Squamous carcinoma showed significantly associated with VEGF-C (P=0.0071** & 0.0071** respectively). Positive VEGF-C staining in cancer cells had more lymphatic vessel (17/68 %) as compared to negative cases (3/30 %) with Chi-Square 8.263, p value= 0.0061**. Also, positive VEGF-C staining had more lymph node associated (9/36%) compared to negative cases (1/10 %) with Chi-Square 13.503, p value= 0.0001**. Conclusion: In conclusion, high expression of vascular endothelial growth factor was noticed in cervical cancer cells and lymph vascular invasion indicating the important role of this marker as prognostic factor for Iraqi cervical cancer. Additionally, these results suggested that VEGF-C promoted cervical cancer metastasis using immunohistochemistry technique. Our findings offer new vision into the role of VEGF-C in cervical cancer development and give potential target for study the lymphangiogensis of tumor in Iraqi women.