Angiogenic and lymphangiogenic profiles in histological variants of papillary thyroid carcinoma.

Vesna Skuletic,Jelena Pantic,Ivan Jovanovic,Nikola Jankovic,Dusica Petrovic,Radan Dzodic,Andra Jevtovic,Gordana D Radosavljevic,Bojana Simovic Markovic,Nebojsa Arsenijevic

doi:10.20452/pamw.3999

Abstract

Papillary thyroid carcinoma (PTC) is a well‑differentiated tumor that occurs in several histological variants whose biological behaviors remain unclear. Angiogenesis and lymphangiogenesis are critical processes that enable tumor progression. The aim of this study was to evaluate the angiogenic and lymphangiogenic phenotypes of PTC, considering the differences between histological variants. Angiogenic and lymphangiogenic profiles were analyzed by determining microvascular density (MVD) and lymphatic vessel density (LVD) in 73 cases of PTC, using immunohistochemistry. To assess the biological markers involved in blood and lymph vessel formation, the expression of vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX‑2), and p27kip1 (p27) was determined. MVD was significantly higher in patients with high‑risk PTC and in those with local extrathyroidal and vascular invasion. Positive VEGF expression was strongly associated with high MVD and age‑related tumor enlargement. The presence of lymph vessel invasion was associated with the expression of either VEGF or COX‑2. The analysis of angiogenesis and lymphangiogenesis in different histological variants of PTC revealed elevated LVD rather than MVD in the follicular variant of PTC (FV‑PTC).Lower MVD was observed in FV‑PTC relative to the classic variant of PTC (CV‑PTC). The frequency of VEGF‑positive tumors was higher in CV‑PTC than in FV‑PTC. A significant association between COX‑2 and p27 expression was observed in FV‑PTC but not in CV‑PTC. These results suggest that VEGF, COX‑2, and p27 may be important biological markers that determine the angiogenic and lymphangiogenic potentials of PTC, particularly between the follicular and classic variants.

Highlights

Papillary thyroid carcinoma (PTC) is a well‐differentiated tumor that occurs in several histological variants whose biological behaviors remain unclear
Papillary thyroid carcinoma angiogenesis in relation to vascular endothelial growth factor and cyclooxygenase-2 expression To better understand the po‐ tential mechanisms of angiogenesis in PTC, we examined the association between micro‐ vascular density (MVD) and the expression of the proangiogenic factors VEGF and cyclooxygenase 2 (COX‐2)
These results suggest that VEGF and COX‐2 are involved in lymph vessel invasion either togeth‐ er or independently

Summary

Introduction

Papillary thyroid carcinoma (PTC) is a well‐differentiated tumor that occurs in several histological variants whose biological behaviors remain unclear. Patients and methods Angiogenic and lymphangiogenic profiles were analyzed by determining micro‐ vascular density (MVD) and lymphatic vessel density (LVD) in 73 cases of PTC, using immunohistochem‐ istry. The analysis of angiogenesis and lymphangiogenesis in different histological variants of PTC revealed elevated LVD rather than MVD in the follicular variant of PTC (FV‐PTC). Conclusions These results suggest that VEGF, COX‐2, and p27 may be important biological markers that determine the angiogenic and lymphangiogenic potentials of PTC, between the follicular and classic variants. PTC has a favorable prognostic outcome and usually occurs in several histological vari‐ ants.[1,2] The molecular profiles that determine the potential aggressive behaviors of different histological variants, the follicular and classical variants, are not fully understood. MVD and LVD indicate an in‐ creased risk for tumor progression and predict disease outcome.[6,7]

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