Keratoacanthoma and squamous cell carcinoma are distinct from a molecular perspective

Abstract

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 (45-fold change: Po0.01) with 908 genes upregulated and 541 genes downregulated. Keratoacanthoma showed 2435 differentially expressed genes in comparison with normal skin (45-fold change: Po0.01) 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.

Keratoacanthoma: a distinct entity?

“…In sum, the recently found TGFβR1 driver mutations in familial KA, Comparative Genomic Hybridization studies, micro array experiments and missing clinical features of a malignant phenotype in KA are in line with our view that KA and SCC are two distinct lesions . Unfortunately, there is still a notable lack of a reliable molecular marker, allowing for the unequivocal distinction of KA from SCC in the laboratory.…”

“…Clinical and morphological distinction between KA and SCC may cause difficulties in certain cases (Tables , and ). Also the question whether KA is a distinct entity or a variant of SCC was discussed controversially until molecular identification of TGFβR1 mutations in Ferguson Smith syndrome and genetic studies clarified that at least familial KA have bona fide an own pathogenetic cause . Indeed, the mutation rate of TGFBR1 for supposed MSSE is about 85–90% (B.…”

Eruptive Keratoacanthomas within a Red Ink Tattoo: A Case Report

“…The finding that skin tumors can be induced by exposure to a carcinogen in those with an oncogenic predisposition has been demonstrated [9]. HPV is one such potential carcinogen that has been associated with KAs.…”

“…Ra et al studied the molecular profiles of KAs in comparison to both regular skin and SCCs and found highly varied expression profiles; 1449 genes were expressed differently between the two diseases. This is compared to actinic keratosis, a purported pre-cursor to SCC, which only varied from SCCs by only 9 genes [9]. Likewise, other studies have supported molecular differentiation between the two in pathways ranging from growth to cellular maturation and apoptosis.…”

Keratoacanthoma en plaque/nodule: A brief report of the clinicopathological features of five cases

“…Keratoacanthoma (KA) is considered to be a benign or borderline squamous proliferative lesion with follicular (infundibular/isthmic) differentiation, that usually shows spontaneous regression, but rarely shows malignant transformation, namely, KA with a squamous cell carcinoma (SCC) component …”