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.
Highlights
The sex-determining region Y (SRY)-related high-mobility-group (HMG)-box family of transcription factors member SOX2 (Sex-determining region Y-box 2) plays a critical role during embryonicCancers 2019, 11, 286; doi:10.3390/cancers11030286 www.mdpi.com/journal/cancersCancers 2019, 11, 286 development and organogenesis, thereby showing a very restricted, and precisely regulated, spatial-temporal expression pattern [1,2]
This study investigates for the first time SOX2 protein expression and gene amplification in the early stages of head and neck squamous cell carcinomas (HNSCC) tumorigenesis using a large series of 94 laryngeal precancerous lesions
This study further and significantly extends these data investigating for the first time SOX2 protein expression and gene amplification in early stages of laryngeal tumorigenesis to ascertain its role in malignant transformation
Summary
The sex-determining region Y (SRY)-related high-mobility-group (HMG)-box family of transcription factors member SOX2 (Sex-determining region Y-box 2) plays a critical role during embryonicCancers 2019, 11, 286; doi:10.3390/cancers11030286 www.mdpi.com/journal/cancersCancers 2019, 11, 286 development and organogenesis, thereby showing a very restricted, and precisely regulated, spatial-temporal expression pattern [1,2]. Amplification of the chromosomal region 3q26-27 is one of the most recurrent genetic alterations in head and neck squamous cell carcinomas (HNSCC) and other carcinomas, which has been associated with tumor progression and poor patient prognosis [11,12]. SOX2 amplification and overexpression has been implicated in many tumor types, but mostly in squamous carcinomas of various localizations (lung, esophagus, head and neck) [13,14,15,16,17,18,19]. The role of SOX2 in HNSCC progression and its impact on prognosis and disease outcome has been subject of intense investigation [7,11,20,21,22,23]. The role of SOX2 in the early stages of HNSCC tumorigenesis and its possible contribution to malignant transformation and acquisition of an invasive phenotype remains unexplored
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
