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Cancers 2019, 11(3), 286; https://doi.org/10.3390/cancers11030286

The Novel Role of SOX2 as an Early Predictor of Cancer Risk in Patients with Laryngeal Precancerous Lesions

1
Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias, University of Oviedo, Avda. Roma, 33011 Oviedo, Spain
2
Ciber de Cáncer, CIBERONC, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain
3
Department of Pathology, Hospital Universitario Central de Asturias, Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, Avda. Roma, 33011 Oviedo, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 18 January 2019 / Revised: 19 February 2019 / Accepted: 22 February 2019 / Published: 1 March 2019
(This article belongs to the Special Issue Targeting Head and Neck Cancer)
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Abstract

The SOX2 gene located at 3q26 is frequently amplified and overexpressed in multiple cancers, including head and neck squamous cell carcinomas (HNSCC). The tumor-promoting activity and involvement of SOX2 in tumor progression has been extensively demonstrated, thereby emerging as a promising therapeutic target. However, the role of SOX2 in early stages of tumorigenesis and its possible contribution to malignant transformation remain unexplored. This study investigates for the first time SOX2 protein expression by immunohistochemistry and gene amplification by real-time PCR using a large series of 94 laryngeal precancerous lesions. Correlations with the histopathological classification and the risk of progression to invasive carcinoma were established. Nuclear SOX2 expression was frequently detected in 38 (40%) laryngeal dysplasias, whereas stromal cells and normal adjacent epithelia showed negative expression. SOX2 gene amplification was detected in 18 (33%) of 55 laryngeal dysplasias. Univariate Cox analysis showed that SOX2 gene amplification (p = 0.046) and protein expression (p < 0.001) but not histological grading (p = 0.432) were significantly associated with laryngeal cancer risk. In multivariate stepwise analysis including age, tobacco, histology, SOX2 gene amplification and SOX2 expression, SOX2 expression (HR = 3.531, 95% CI 1.144 to 10.904; p = 0.028) was the only significant independent predictor of laryngeal cancer development. These findings underscore the relevant role of SOX2 in early tumorigenesis and a novel clinical application of SOX2 expression as independent predictor of laryngeal cancer risk in patients with precancerous lesions beyond current WHO histological grading. Therefore, targeting SOX2 could lead to effective strategies for both cancer prevention and treatment. View Full-Text
Keywords: cancer risk assessment; larynx; dysplasia; SOX2; immunohistochemistry; gene amplification cancer risk assessment; larynx; dysplasia; SOX2; immunohistochemistry; gene amplification
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Granda-Díaz, R.; Menéndez, S.T.; Pedregal Mallo, D.; Hermida-Prado, F.; Rodríguez, R.; Suárez-Fernández, L.; Vallina, A.; Sánchez-Canteli, M.; Rodríguez, A.; Fernández-García, M.S.; Rodrigo, J.P.; García-Pedrero, J.M. The Novel Role of SOX2 as an Early Predictor of Cancer Risk in Patients with Laryngeal Precancerous Lesions. Cancers 2019, 11, 286.

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