Keratoacanthoma is a controversial entity. Some consider
keratoacanthoma as a variant of
squamous cell carcinoma, whereas others see it as a distinct self-resolving squamoproliferative lesion. Our objective is to examine the relationship of
keratoacanthoma with
squamous cell carcinoma and normal skin by using
DNA microarrays.
DNA microarray studies were performed on
formalin-fixed and
paraffin-embedded blocks from ten cases of actinic
keratoacanthoma utilizing the U133plus2.0 array. These results were compared with our previously developed microarray database of ten
squamous cell carcinoma and ten normal skin samples.
Keratoacanthoma demonstrated 1449 differentially expressed genes in comparison with
squamous cell carcinoma (>5-fold change: P<0.01) with 908 genes upregulated and 541 genes downregulated.
Keratoacanthoma showed 2435 differentially expressed genes in comparison with normal skin (>5-fold change: P<0.01) with 1085 genes upregulated and 1350 genes downregulated. The most upregulated genes, comparing
keratoacanthoma with normal skin included MALAT1, S100A8, CDR1, TPM4, and CALM1. The most downregulated genes included SCGB2A2,
DCD, THRSP, ADIPOQ,
adiponectin, and ADH1B. The molecular
biological pathway analysis comparing
keratoacanthoma with normal skin showed that cellular development, cellular growth and proliferation, cell death/apoptosis, and cell cycle pathways are prominently involved in the pathogenesis of
keratoacanthoma. The most enriched canonical pathways were
clathrin-mediated endocytosis signaling, molecular mechanisms of
cancer and
integrin signaling. The distinctive gene expression profile of
keratoacanthoma reveals that it is molecularly distinct from
squamous cell carcinoma. The molecular pathways and genes differentially expressed in comparing
keratoacanthoma with normal skin suggest that
keratoacanthoma is a
neoplasm that can regress due to upregulation of the cell death/apoptosis pathway.