FGF-2, FGFR-1, PI3K, Akt and COX-2 expression in Oral Leucoplakia, primary and metastatic Oral Squamous Cell Carcinoma

Abstract

Oral Squamous Cell Carcinoma (OSCC) accounts for the great majority of the malignancies in the oral cavity, with 300,000 new cases for year, representing one of the sixth most common types of Cancer in the world. The prognostic perspectives for patients are cloudy, with a 5-years survival rate of only 50% after diagnosis, with small advances in the past three decades. Despite the advances in molecular pathology, no tumor biomarkers associated with oral Cancer progression and prognosis have been approved for clinical use, as occurs in other types of Cancer. Oral Leucoplakia (OL) is the most common Oral Potentially Malignant Disorder (OPMD), affecting 1% of the global population, with malignant transformation rates ranging from 2 to 5%. FGF-2 and FGFR-1 immunoexpression is correlated with worse prognosis and more invasive tumors in patients with OSCC. Changes in the FGF/FGFR pathway can activate a downstream signaling via PI3K/Akt. Akt is an inactive cytosolic protein, activated through phosphorylation via PI3K, blocking several apoptotic proteins. It has been proved that Akt directly regulates COX-2 gene and protein expression. Similarly, COX-2 overexpression is associated with more aggressiveness in different types of Cancer, including breast, colon, lung, and head and neck tumors. From all the evidence given above, the main objectives of this project are: (1) evaluate the immunoexpression of FGF-2, FGFR-1, PI3K, Akt, and COX-2 in oral leucoplakia, primary and metastatic OSCC; and (2) study how the FGFR-1 gene silencing affects the biological behavior of primary and metastatic OSCC cell lines in vitro and in vivo. (AU)