Proliferative ability and accumulation of cancer stem cells in oral submucous fibrosis epithelium

Abstract

ObjectivesThe driving force of the malignant transformation of epithelial cells during oral submucous fibrosis (OSF) is an unsettled debate. We hypothesized that the expression and accumulation of cancer stem cells (CSCs) are accompanied by epithelial atrophy in OSF.Materials and MethodsThe expression levels of Ki67 (proliferation marker), SOX2, and Bmi1 (CSC marker) in the epithelium during the early, middle, and late stages of OSF were measured by immunohistochemistry. At the same time, we focused on the expression of three proteins in OSF patients with benign hyperkeratosis and epithelial dysplasia.ResultsThe clinical cohort study showed upregulated expression of the proliferation‐associated protein Ki67 in atrophic epithelium in patients with OSF. The expression levels of SOX2 and Bmi1 showed an increasing trend in the progression of OSF. Ki67, SOX2, and Bmi1 were highly expressed in OSF tissues with dysplasia. Moreover, the three proteins were located at the epithelial and mesenchymal junctions, and their expression showed a positive correlation with each other.ConclusionThe results suggest that CSC accumulation could be accompanied by epithelial atrophy during OSF, which may be responsible for the driving forces for OSF carcinogenesis.

Immunohistochemical biomarkers in oral submucous fibrosis: A scoping review

“…Co‐expression of two pairs of biomarkers, Ki67‐p16, and FGF2‐FGF2R was significantly increased in malignant transformation of OSF and OSCC cases 20,24 . Furthermore, α‐SMA, Ki67, CD105, p16, SOX2, Bmi, FGF2, FGFR2, ANXN A4, FLNA, and FGA were studied prospectively in studies where OSF cases were followed up for malignant transformation 19,20,22–24,27 . (Table 2)…”

“…20,24 Furthermore, α-SMA, Ki67, CD105, p16, SOX2, Bmi, FGF2, FGFR2, ANXN A4, FLNA, and FGA were studied prospectively in studies where OSF cases were followed up for malignant transformation. 19,20,[22][23][24]27 (Table 2)…”

“…α‐SMA, 23 podoplanin, 41 cyclooxygenase‐2 (COX2), 42 α‐enolase, 43 p53, 24 p63, 44‐46 ΔNp63, 44 p16, 24 Ki67, 23,27 cytokeratin (CK‐5/6), 44 VEGF, 47 CD105, 23,45,47 vimentin, 48 PCNA, 49 caspase‐3, 50 SOX2, Bmi1, 27 and cytoplasmic expression of E‐cadherin and β‐catenin 49 were upregulated in OSF with dysplasia compared with OSF without dysplasia and normal subjects. Loss of membranous E‐cadherin and β‐catenin was evident in OSF with moderate and severe dysplasia 45–47 …”

“…This scoping review gives an overview of studies on immunohistochemical biomarkers in OSF. The lacunae/deficiencies in the published studies include the following: Heterogeneity in patient characteristics and the absence of survival data restrict the synthesis of data available into a systematic review with/ without meta‐analysis. Paucity of longitudinal studies: only six studies were prospectively followed for malignant transformation 19,20,22–24,27 Use of visual scoring methods that are subjective. Categorical qualitative assessment. Lack of sample size justification. Mismatch in the number of cases and controls, increasing the chances of type I error. Exclusion criteria were not mentioned in 30% ( n = 26) of articles. None of the articles discuss the statistical confounders which can be controlled either by stratified analysis or by multivariate analysis. …”

Pathological Investigations And Correlation Research of Microfibrillar-Associated Protein 4 And Tropoelastin In Oral Submucous Fibrosis

“…Oral Submucous Fibrosis (OSF) is a chronic, irreversible, persistent progressive, potentially malignant disease with the malignant transformation rate of 7% -30% [1][2][3]. Currently, the extremely significant accumulation of the extracellular matrix (ECM) both in OSF and other fibrotic diseases has attracted proverbially attention.…”