Affiliations: Department of Otolaryngology, Hospital Universitario Central de Asturias, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain | Department of Otolaryngology, Hospital Valle del Nalón, Asturias, Spain | Department of Pathology, Universidad de Oviedo, Spain
Note: [] Corresponding author: Dr. Marta Alonso Guervós, Department of Otolaryngology, IUOPA, Laboratory N° 2-ORL, Edf. Hospital Covadonga, 1°-Centro Hospital Universitario Central de Asturias, Celestino Villamil s/n, 33006 Oviedo (Asturias), Spain. Tel.: +34 985 107956; Fax: +34 985 108015; E-mail: maguervos@yahoo.es
Abstract: Background: Lymph node metastasis is the mayor cause of mortality in patients with head and neck squamous cell carcinomas (45%). The genetic changes underlying metastasis are still largely unknown and genetic markers to predict lymph node positivity still need to be found. The aim of this study was to search such markers by using Multiplex Ligation-dependent Probe Amplification (MLPA), a semi-quantitative PCR technique to detect gene copy number alterations. Methods: Thirty-seven genes were analysed by MLPA in 34 larynx and 22 pharynx carcinomas. Results: Losses of CDKN2A (9p21) and MLH1 (3p22) and gains of CCND1, EMS1 (both at 11q13), RECQL4 and PTP4A3 (both at 8q24) were the most frequent aberrations in both larynx and pharynx carcinomas. Amplifications were detected at EMS1, CCND1 and ERBB2 (17q21). A correlation between loss of N33 (8p22) and poor survival was found (p=0.02). Gain of EMS1 had the same relation with survival but not significant (p=0.08). Lymph node positive tumors presented a specific pattern of genetic alterations, with losses of N33, STK11 (19p13) and TP53 (17p13), the latter especially in larynx tumors. Conclusion: We propose that these 3 genes might play a role in the development of metastasis in larynx and pharynx squamous cell carcinomas.
