Genotypic and phenotypic characterization of keratoacanthoma and possible distinguishing features from cutaneous squamous cell carcinoma

Keratoacanthoma (KA) is a benign keratinocytic neoplasm localized to the sun-exposed skin of elderly persons that develops rapidly and regresses spontaneously. The early proliferative phase has similar histopathological features to cutaneous squamous cell carcinoma (cSCC). This thesis aims to provide a better understanding of the biology of young and old phase KA based on histopathological age and clinical age given by the patients, as well as to differentiate KA from cSCC, based on phenotypic and genotypic characteristics. A substantially higher proportion of Tp53 mutations (approx. 40%) were detected in KA compared to previous studies. Considerably higher numbers of lesions that lacked Tp53 mutations in the old KA subgroup suggest a possible role for wild type p53 protein in KA regression. KA has a life cycle reminiscent of the hair cycle, where activation of the Wnt signaling pathway is vital for regeneration in the anagen phase. We did not find differential expression of the Wnt signaling pathway proteins between young and old human KAs, in contrast to the results from an experimentally-induced murine KA model that demonstrated an active Wnt signaling pathway in young KAs and suppression of the same pathway in old KAs. Aberrant expression of spindle proteins is related to carcinogenesis. Significantly higher levels of the spindle proteins Aurora-A, Mad2, and BUBR1 were seen in cSCC compared to KA, suggesting a potential difference between KA and cSCC. In summary, this thesis work has provided new insights into KA development and regression, and suggests that KA and cSCC are two distinct entities