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Molecularly Enriched Pathways and Differentially Expressed Genes Distinguishing Cutaneous Squamous Cell Carcinoma From Pseudoepitheliomatous Hyperplasia

Ra, Seong H. MD*,†; Su, Albert MD*; Li, Xinmin PhD*; Binder, Scott MD*

Diagnostic Molecular Pathology: March 2013 - Volume 22 - Issue 1 - p 41–47
doi: 10.1097/PDM.0b013e3182707894
Original Articles

Introduction: Cutaneous squamous cell carcinoma (SCC) is one of the most commonly diagnosed nonmelanoma skin cancers. Occasionally, the diagnosis can be challenging as there are many simulating preneoplastic and reactive squamous lesions. One of the most difficult lesions to differentiate from SCC is pseudoepitheliomatous hyperplasia (PEH). The objective of our study is to differentiate cutaneous SCC from PEH using gene expression microarrays and examine the enriched molecular pathways and genes.

Design: DNA microarray studies were performed on formalin-fixed and paraffin-embedded blocks of the skin: 10 cases of SCCs and 10 cases of PEHs using the U133 plus 2.0 array.

Results: A total of 703 differentially expressed genes were identified between SCCs and PEHs (>2-fold change, P<0.05) including multiple upregulated S100 calcium-binding proteins and downregulated homeobox genes. Functional analysis of these genes suggests that oxidative phosphorylation, mitochondrial dysfunction and the polyamine regulation pathways are involved in the pathogenesis of SCC.

Conclusions: The distinctive gene expression profile of SCC and PEH offers the ability to use DNA microarrays to distinguish between them by an objective molecular measure. The molecular pathways and differentially expressed genes provide an insight into the pathogenesis of SCCs and may serve as future targets for therapeutic intervention.

*Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles

San Diego Pathology Medical Group Inc., San Diego, CA

The authors declare no conflict of interest.

Reprints: Seong Ra, MD, San Diego Pathology Medical Group Inc., 7592 Metropolitan Drive, Suite 405, San Diego, CA 92108 (e-mail:

© 2013 Lippincott Williams & Wilkins, Inc.