Combined PIK3CA and SOX2 Gene Amplification Predicts Laryngeal Cancer Risk beyond Histopathological Grading

Author:

Montoro-Jiménez Irene12,Granda-Díaz Rocío12,Menéndez Sofía T.12,Prieto-Fernández Llara12,Otero-Rosales María12,Álvarez-González Miguel1,García-de-la-Fuente Vanessa1,Rodríguez Aida1,Rodrigo Juan P.12ORCID,Álvarez-Teijeiro Saúl12ORCID,García-Pedrero Juana M.12ORCID,Hermida-Prado Francisco12ORCID

Affiliation:

1. Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias (IUOPA), University of Oviedo, 33011 Oviedo, Spain

2. CIBERONC, Instituto de Salud Carlos III, 28029 Madrid, Spain

Abstract

The PIK3CA and SOX2 genes map at 3q26, a chromosomal region frequently amplified in head and neck cancers, which is associated with poor prognosis. This study explores the clinical significance of PIK3CA and SOX2 gene amplification in early tumorigenesis. Gene copy number was analyzed by real-time PCR in 62 laryngeal precancerous lesions and correlated with histopathological grading and laryngeal cancer risk. Amplification of the SOX2 and PIK3CA genes was frequently detected in 19 (31%) and 32 (52%) laryngeal dysplasias, respectively, and co-amplification in 18 (29%) cases. The PIK3CA and SOX2 amplifications were predominant in high-grade dysplasias and significantly associated with laryngeal cancer risk beyond histological criteria. Multivariable Cox analysis further revealed PIK3CA gene amplification as an independent predictor of laryngeal cancer development. Interestingly, combined PIK3CA and SOX2 amplification allowed us to distinguish three cancer risk subgroups, and PIK3CA and SOX2 co-amplification was found the strongest predictor by ROC analysis. Our data demonstrate the clinical relevance of PIK3CA and SOX2 amplification in early laryngeal tumorigenesis. Remarkably, PIK3CA amplification was found to be an independent cancer predictor. Furthermore, combined PIK3CA and SOX2 amplification is emerging as a valuable and easy-to-implement tool for cancer risk assessment in patients with laryngeal precancerous lesions beyond current WHO histological grading.

Funder

Instituto de Salud Carlos III

CIBERONC

European Union

Instituto de Investigación Sanitaria del Principado de Asturias

Fundación Bancaria Cajastur-IUOPA

Universidad de Oviedo

Principado de Asturias

Spanish Ministry of Education

Publisher

MDPI AG

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