Basal cell carcinoma and pilomatrixoma mirror human follicular embryogenesis as reflected by their differential expression patterns of SOX9 and β-catenin

Abstract

Background: The current classification schemes of adnexal tumours are predominantly based on morphological and immunophenotypical similarities to adult skin structures, whereas a link between the embryology of the skin and the histogenesis of adnexal tumours has been largely neglected.

Objective: To describe the expression patterns of two proteins with proven relevance for hair follicle homeostasis (SOX9 and β-catenin) during human cutaneous embryogenesis and to compare the findings with their expression in basal cell carcinoma (BCC) and pilomatrixoma.

Methods: Immunohistochemical evaluation with monoclonal antibodies against SOX9 and β-catenin was carried out in embryonic and adult human scalp skin, and BCC and pilomatrixoma samples.

Results: We found that the expression patterns of SOX9 and β-catenin during human hair follicle embryogenesis mirror the patterns in BCC and pilomatrixoma in spatial distribution within the various follicular subcompartments. Beginning with the hair peg stage, nucleocytoplasmic immunoreactivity of β-catenin is exclusively confined to the emerging matrix (comparable to pilomatrixoma), whereas SOX9 is restricted to the primordial outer root sheath (comparable to BCC).

Conclusions: An appropriate immunophenotyping validated within the conceptual framework of cutaneous developmental biology allows a logical classification of adnexal neoplasms. Expanding this approach further has the potential to revise the current classification schemes so that not only BCC and pilomatrixoma but all adnexal tumours can be categorized logically.