Expression of VEGF-A and VEGF-C and its correlation with clinical-pathological characteristics and molecular markers associated with the pathogenesis of papillary thyroid carcinoma

Abstract

The well-differentiated thyroid carcinomas are the most common endocrine neoplasia, being the papillary (PTC) subtype the most frequent. The molecular aspects related to this pathology are well studied, where the main genetic alterations are BRAFV600E activating mutation, mutations in the gene NRAS and the RET/PTC fusion. All these genetic events cause the constitutive activation of the MAPK pathway. Even though they participate in the same signaling pathway, these mutations can activate different substrates, and, in that way, the global genetic expression profile can differ between tumors. Among the genes modulated by the MAPK pathway, it has been suggested that this signaling cascade highly influences the expression of factors related to inflammation, as for example VEGF-A. The VEGF-A is very important in angiogenesis and in the recruitment of inflammatory cells, being expressed above normal levels in many carcinomas, including PTC. Another member of this family of proteins is VEGF-C, which is important in lymphangiogenesis. In PTC, there is a higher prevalence of metastasis in lymph nodes than in any other place, indicating that VEGF-C may play an important role in the process. One molecular marker that has been found in our laboratory, the CXCL-14, is a chemokine that helps in the recruitment of immune cells. This chemokine is a lot more expressed in PTC tumors than in normal tissue and follicular subtype. In this way, we intend to analyze the correlation of VEGF-A and VEGF-C expression with the different clinical-pathological aspects and the most important molecular aspects, such as BRAFV600E status, NRAS mutation and RET/PTC fusion, but also with molecular aspects related directly with inflammation such as expression of CXCL-14, it's receptor CXCR-4, and another chemokine with the same receptor, CXCL-12.