SOX2 Expression Is an Independent Predictor of Oral Cancer Progression

Abstract

Potentially malignant oral lesions, mainly leukoplakia, are common. Malignant transformation varies widely, even in the absence of histological features such as dysplasia. Hence, there is a need for novel biomarker-based systems to more accurately predict the risk of cancer progression. The pluripotency transcription factor SOX2 is frequently overexpressed in cancers, including oral squamous cell carcinoma (OSCC), thereby providing a link between malignancy and stemness. This study investigates the clinical relevance of SOX2 protein expression in early stages of oral carcinogenesis as a cancer risk biomarker, and also its impact on prognosis and disease outcome at late stages of OSCC progression. SOX2 expression was evaluated by immunohistochemistry in 55 patients with oral epithelial dysplasia, and in 125 patients with OSCC, and correlated with clinicopathological data and outcomes. Nuclear SOX2 expression was detected in four (7%) cases of oral epithelial dysplasia, using a cut-off of 10% stained nuclei, and in 16 (29%) cases when any positive nuclei was evaluated. Univariate analysis showed that SOX2 expression and histopathological grading were significantly associated with oral cancer risk; and both were found to be significant independent predictors in the multivariate analysis. Nuclear SOX2 expression was also found in 49 (39%) OSCC cases, was more frequent in early tumor stages and N0 cases, and was associated with a better survival. In conclusion, SOX2 expression emerges as an independent predictor of oral cancer risk in patients with oral leukoplakia. These findings underscore the relevant role of SOX2 in early oral tumorigenesis rather than in tumor progression.

An anatomical perspective on clinicopathological characteristics and treatment outcomes of dorsal and ventrolateral tongue leukoplakia after carbon dioxide laser surgery

“…Approximately 300,000 new cases of oral squamous cell carcinoma occur annually and the treatment outcomes and survival are highly stage-dependent [ 1 , 2 ]. Although oral cancers can occur de novo, large number of oral cancers are derived from oral potentially malignant disorders.…”

Macrophages in Oral Carcinomas: Relationship with Cancer Stem Cell Markers and PD-L1 Expression

“…Accordingly, for analytical purposes, OSCC patients were dichotomized into two groups: relevant versus nonrelevant PD-L1 expression, based on the established cut-off point of 10% of stained tumor cells. NANOG expression was scored as negative (absence of staining, score 0), weak to moderate (some cytoplasmic staining in dysplastic areas, score 1), and strong protein expression (intense and homogeneous cytoplasmic staining in dysplastic areas, score 2), and SOX2 expression was evaluated as the percentage of tumor cells with positive nuclear staining, following previously described methods [ 12 , 13 ]. For statistical purposes, NANOG staining was dichotomized as negative (score 0) versus positive expression (scores 1–2).…”

“…However, the functional role of TAMs in OSCC is poorly understood, and the possible relationship between TAM infiltration and CSC phenotypes has not been investigated yet in oral carcinogenesis [ 11 ]. Among the numerous CSCs markers, NANOG and SOX2 have recently been identified as predictors of oral cancer risk in patients with oral precancerous lesions [ 12 , 13 ].…”

Oral tongue leukoplakia: analysis of clinicopathological characteristics, treatment outcomes, and factors related to recurrence and malignant transformation

“…In comparison with the normal oral mucosa, OPMDs, which encompass a number of lesion types, including leukoplakia, erythroplakia, oral lichen planus, oral submucous fibrosis, and other miscellaneous lesions, are characteristics of an increased risk of malignant transformation [1,9,10]. Oral leukoplakia (OLK) is the most common type of OPMD and has been widely studied [2,5,[9][10][11][12][13]. The risks of malignant transformation of OLK have always been the focus of clinical attention.…”