Keratoacanthoma and squamous cell carcinoma are distinct from a molecular perspective

Seong H. Ra, Albert Su, Xinmin Li, Jaime Zhou, Alistair J. Cochran, Rajan P. Kulkarni, Scott W. Binder

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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 (>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.

Original languageEnglish (US)
Pages (from-to)799-806
Number of pages8
JournalModern Pathology
Volume28
Issue number6
DOIs
StatePublished - Jun 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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