Aberrant expression of S100A6 and matrix metalloproteinase 9, but not S100A2, S100A4, and S100A7, is associated with epidermal carcinogenesis

Background: S100 proteins belong to a family of calcium-binding proteins that regulate cell proliferation and differentiation. Despite our growing knowledge about the biology of S100 proteins in some human cancers, little is known about the expression of S100 family members in epidermal tumors and their clinical significance. Objective: To determine the expression of S100A2, S100A4, S100A6, S100A7, as well as matrix metalloproteinases 9 (MMP9) in a spectrum of epidermal tumors with benign and malignant characteristics. Methods: Immunohistological staining was performed for S100A2, S100A4, S100A6, S100A7, and MMP9 in 101 cases of various types of epidermal tumors, viz., squamous cell carcinoma (SCC), Bowen's disease (BD), actinic keratosis (AK), basal cell carcinoma (BCC), keratoacanthoma (KA), and seborrheic keratosis (SK). Thirteen specimens of normal skin (NS) served as control. Results: S100A2, S100A6, and S100A7 positive immunostaining was variably observed in different epidermal tumors. S100A4 staining was not observed in any epidermal tumors, but was clearly visible in dendritic cells. MMP9 immunostaining was positive only in 22/26 (84.62%) of SCC and 2/15 (13.33%) of BD cases. Expression of S100A2, S100A6, and S100A7 was increased in tumor cells compared to NS. However, only S100A6 expression was significantly associated with malignant transformation of epidermal tumors. Moreover, S100A6 expression was correlated with MMP9 expression in metastatic SCC. Conclusions: Epidermal tumors show increased expression of S100A2 and S100A7 proteins. S100A4 may be a useful and distinct marker for epidermal dendritic cells. Expression of S100A6 and MMP9 in combination is associated with the development of SCC.