EPCAM GENE EXPRESSION IS A BIOMARKER FOR LYMPH NODE METASTASIS IN LARYNGEAL SQUAMOUS CELL CARCINOMA

INTRODUCTION AND OBJECTIVES: Laryngeal cancer is a high incident disease worldwide, mainly in low socioeconomic development countries such as Brazil. Laryngeal squamous cell carcinoma (LSCC) is the main histological subtype, accounting for more than 85% of the cases and is strictly associated with tobacco smoking. Additionally, the LSCC prognosis rate was not improved in the last 40 years. LSCC is a heterogeneous tumor, both at the clinical and molecular levels, and this feature was already associated with tumor stem cells in other sites, such as breast and lung carcinomas. Recently we demonstrated that ALCAM expression, a marker of tumor stem cells, is an independent prognostic factor of LSCC patients. Also, its expression was correlated with other stem cell markers, as EPCAM. EPCAM encodes the "Epithelial Cell Adhesion Molecule" expressed in normal epithelial cells and gastrointestinal carcinomas and acts as a homotypic calcium-independent cell adhesion molecule. This protein is being used as a target for immunotherapy treatment of human carcinomas and low information was already published about EPCAM in LSCC. Thus, this study aimed to evaluate the expression of EPCAM in LSCC, associating its expression with patients’ pathological and clinical characteristics. MATERIAL AND METHODS: We evaluated the EPCAM expression in 34 LSCC and adjacent mucosa paired samples from INCA patients, using the RT-qPCR method. Samples were analyzed in duplicate and GAPDH was the housekeeping gene. Following, gene expression was associated with clinical and pathological features, and statistical analyzes were performed in GraphPad Prism 5.0. RESULTS: The EPCAM gene was overexpressed in LSCC samples in comparison to paired adjacent mucosa (p= 0,0230) and its high expression was observed in samples presenting angiolymphatic invasion (p = 0,0247), lymph node metastasis (pN) (p = 0,0146) and high grade of lymph node metastasis (p = 0,0320). Besides, higher EPCAM fold change expression levels (tumor/adjacent mucosa) were associated with tobacco smoking usage (p= 0,0404) and angiolymphatic invasion (p= 0,0428). CONCLUSION: Our data show that alterations in EPCAM expression are a common event in LSCC and are associated with several features of this tumor. Besides, EPCAM overexpression was associated with lymph node metastases, suggesting that its expression could be used as a biomarker for metastatic disease, which is a characteristic of tumor aggressiveness.