S100A protein expression in the distinction between lentigo maligna and pigmented actinic keratosis

Lentigo maligna (LM), a type of malignant melanoma in situ, and pigmented actinic keratosis (PAK) may have similar clinical appearances but are different in prognosis and treatment. Diagnosis is established by skin biopsy. In certain cases, microscopic features may be very similar in both entities, making it difficult to determine whether the pigmented atypical cells are keratinocytes or melanocytes. Immunohistochemical markers can be useful for the identification of melanocytes in these cases. There are limitations to the use of some standard immunohistochemistry markers, however. S100 proteins are a varied group of proteins that are of special interest because of their dysregulated expression in neoplastic disorders. Their expression is changed during malignant transformation, progression, and/or metastasis in various cell lines and tumors, including melanomas. Our study analyzed the expression of several of the S100 protein subtypes (S100A2, S100A6, and S100A8/A9 or A12) in 38 LM cases and 44 PAK cases to define their potential value in the distinction between these entities together with their role in the development of early malignant melanoma of the skin. The results showed an upregulation of S100A2 protein in atypical keratinocytes in PAK and in normal keratinocytes adjacent to melanoma cells in LM. There was also an upregulation of S100A8/A9 or A12 protein, as detected by the antibody MAC387, in normal keratinocytes adjacent to both atypical keratinocytes and melanocytes in PAK and LM, respectively. There were statistically significant differences in the level of positive cells and in the pattern of immunoreactivity for anti-S100A2 and MAC387 in each entity, however. Moreover, the findings of our study support the notion that melanocyte-keratinocyte interactions are abnormal in both of these disease entities and may be involved in their progression.