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.
Highlights
Squamous cell carcinoma (SCC) of the oral cavity (OSCC) afflicts about 300,400 new cases and causes 145,400 deaths worldwide each year [1], with a predilection for South Asian and Southeast Asian populations [2]
Metastases to neck lymph nodes occur in 40% of cases, which remain the main factor associated with poor prognosis [4]
Arnold et al [27] reported that epithelial adult stem cells expressing SOX2 may be residual stem niches that originate from embryonic SOX2-positive tissue progenitors
Summary
Squamous cell carcinoma (SCC) of the oral cavity (OSCC) afflicts about 300,400 new cases and causes 145,400 deaths worldwide each year [1], with a predilection for South Asian and Southeast Asian populations [2]. OSCC shows an aggressive growth pattern with a high degree of local invasiveness and a propensity to metastasize to the cervical lymph nodes, even in early stages. Metastases to neck lymph nodes occur in 40% of cases, which remain the main factor associated with poor prognosis [4]. Between 26% and 80% of patients with early-stage OSCC develop locoregional recurrence or distant metastasis [4]. The prognosis of this disease remains dismal, with a five-year survival rate at around 55%–60% [2]
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