Stem cell markers (cytokeratin 15, cytokeratin 19 and p63) in in situ and invasive cutaneous epithelial lesions

Abstract

The inherent longetivity of stem cells causes them to be susceptible to multiple genetic hits. Thus, it is not surprising that stem cells are implicated in the etiopathogenesis of select cutaneous neoplasms. However, most studies to date are restricted to the use of a single marker (p63, cytokeratin-15 or cytokeratin-19) and do not appear to compare distribution of stem cell markers in a spectrum of cutaneous in situ versus invasive epithelial malignancies. In this study, we evaluate expression of cytokeratin-15, cytokeratin-19, and p63 in a series of primary cutaneous epithelial lesions that include actinic keratosis (n=29), squamous cell carcinoma in situ (n=30), bowenoid papulosis (n=15) and squamous cell carcinoma, well differentiated (n=29) in order to evaluate the role of stem cell marker expression in the grading and development of in situ and invasive malignancies. For cytokeratin-15, expression was retained in actinic keratosis (38%), squamous cell carcinoma in situ (53%) and bowenoid papulosis (60%) but appeared to be lost in squamous cell carcinoma (3%) with statistically significant differences observed between groups that retained versus those that did not (P<0.05 for all three); for cytokeratin-19, patchy yet basal expression was noted in actinic keratosis (21%), patchy and suprabasal expression was noted in squamous cell carcinoma in situ (37%), bowenoid papulosis (13%) and squamous cell carcinoma (24%) with no statistically significant differences between groups; for p63, expression was retained in actinic keratosis (90%), squamous cell carcinoma in situ (87%), bowenoid papulosis (60%) and squamous cell carcinoma (100%) with no statistically significant differences between groups. In summary, our findings expand the neoplasms which involve stem cells to include cutaneous epithelial malignancies. Differential localization of each of these markers argues in favor of stem cell heterogeneity.