SOX2 Is a Potential Diagnostic Biomarker and Anticancer Target in Cutaneous Squamous Cell Carcinoma in Dystrophic Epidermolysis Bullosa: A Case Series Study

A serious complication in epidermolysis bullosa (EB), particularly in recessive dystrophic EB, is the development of aggressive cutaneous squamous cell carcinoma with a high risk for metastasis and poor survival outcomes. The current standard of care is insufficient, and there is a critical need for safe and effective management options for this life-threatening complication in EB. Moreover, the pathophysiologic processes behind the aggressiveness of EB-associated cutaneous squamous cell carcinoma (EB-cSCC) remain elusive. Especially little is known about genetic drivers specific for EB-cSCC, and information about the molecular profile of these highly malignant tumors could lead to novel insights about the underlying pathogenesis. In addition, EB-associated pseudoepitheliomatous hyperplasia (EB-PEH) is difficult to distinguish from EB-cSCC histologically and could be a premalignant precursor of EB-cSCC. Therefore, the aim of this study was to conduct gene expression profiling to detect potentially diagnostic biomarkers and anticancer targets in EB-cSCC and explore the potential role of EB-PEH in the tumorigenesis of EB-cSCC. We performed mRNA expression analysis and immunohistochemistry on formalin-fixed, paraffin-embedded tissue samples of EB-cSCCs (n = 8), non-EB-cSCCs (n = 10), and EB-PEHs (n = 7). The results revealed upregulation of <i>SOX2</i> mRNA expression in EB-cSCCs compared with that in non-EB-cSCCs, albeit in this study, the sample size was small, and cases and controls were not age matched, which may limit interpretation of our findings. In addition, immunohistochemical staining showed increased SOX2 protein expression in EB-cSCCs compared with that in non-EB-cSCCs. SOX2 protein expression was also observed in EB-PEH, with 1 case showing a transition from SOX2-negative to SOX2-positive cells, indicating the possible initiation of an EB-cSCC in situ. Further validation of the study results, including mechanistic studies, is needed before the utility of SOX2 as a biomarker can be assessed. However, these findings propose that SOX2 may play a role in the development of aggressive EB-cSCC and could serve as a potential biomarker of progression from benign EB-PEH to EB-cSCC.