Spalt-like transcription factor 4 expression in oral epithelial dysplasia and oral squamous cell carcinoma: An immunohistochemical appraisal.

Abstract

Background: Spalt-like transcription factor 4 (SALL4) is a stem cell marker that plays a critical role in maintaining the pluripotency and self-renewal of embryonic and hematopoietic stem cells. Only a few studies have been done to apprehend the expression of SALL4 in the potentially malignant oral lesion (leukoplakia with dysplasia) and oral squamous cell carcinoma (OSCC).

Aim: The aim of this study is to evaluate the expression of SALL4 in leukoplakia with dysplasia and OSCC and to correlate the expression of the marker (SALL4) with the various clinicopathological parameters and patient outcome.

Materials and methods: Immunohistochemistry for SALL4 protein was performed on 140 cases: those histopathologically confirmed cases of leukoplakia with dysplasia (n = 30) and OSCC (n = 110). Ten cases of nonepithelial neoplasm (fibroepithelial hyperplasia and excised tissue surrounding impacted third molars) were taken as control. Statistical analyses were applied to evaluate correlations between SALL4 overexpression and clinicopathological features of leukoplakia and OSCC. Survival rates were analyzed using Kaplan-Meier method.

Results: SALL4 positivity was observed to be higher (P = 0.001) in the tumor cells of OSCC with Immuno Reactive Score (IRS) ranging from 0 to 9. Poorly differentiated squamous cell carcinoma (SCC) had paramount higher expression with a median IRS of 6. Similar IRS and above (IRS, 6-9) was observed in Stage I (five cases), which recurred and well-differentiated cases with metastasis (four cases) while in leukoplakia with dysplasia the SALL4 expression was weak with a range of 2-4.

Conclusions: SALL4 being one of the cancer stem cell molecules plays an important role in the progression of oral cancer, which was evident in this study. This could also account for aggressive clinical behavior. Follow-up of these patients would relate this molecule could be responsible for cancer relapse. Patients diagnosed to have oral epithelial dysplasia had a low expression of SALL4, are under follow-up, although seven cases did transform to SCC. Thus, we conclude, SALL4 may be of prognostic relevance, but in oral epithelial dysplasia, it requires further investigations.