The role of novel prognostic markers PROX1 and FOXC2 in carcinogenesis of oral squamous cell carcinoma.

OBJECTIVE: Oral squamous cell carcinoma is the most common malignant tumor of the head and neck regions and accounts for more than 90% of cancers in the oral cavity. The angiogenesis, lymphangiogenesis and epithelial mesenchymal transition are known to be pivotal for tumor progression and metastasis. In the last decade, much data has been generated concerning the molecular mechanisms of angiogenesis, lymphangiogenesis and its significance in pathological conditions. The main angiogenic and lymphangiogenic factors have been identified as vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor receptor 2 (VEGFR-2), forkhead box (FOX) C2 while vascular endothelial growth factor C/D (VEGF-C/D), vascular endothelial growth factor receptor 3 (VEGFR-3), Prospero homeobox 1 (PROX1), LYVE-1, podoplanin, Tie/Angioprotein (Ang) 2 and EphrinB2 respectively. PROX1 is a mammalian homologue of Drosophilia homeobox protein, prospero and important for the embryonic development of many mammalian tissues. It has been suggested that it plays various tissue dependent functional roles, which reflects both oncogenic potential and a tumor suppressive role. The exact role in OSCC remains controversial. FOXC2 is a transcription factor belongs to large family of protein, forkhead box. It has been shown to be involved in cancer angiogenesis, proliferation and metastasis through its induction of epithelial-to-mesenchymal transition while its significance in OSCC remains unknown. Based on these data, this article reviews the role of novel prognostic factors PROX1 and FOXC2 in carcinogenesis of OSCC so that they might be considered as an attractive therapeutic target for both tumor associated blood vessels, lymphatic vessels and tumor cells.