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Archives of Dermatology
Year: 2010  |  Volume: 146  |  Issue: 3  |  Page No.: 288 - 293

Gene Expression Patterns of Normal Human Skin, Actinic Keratosis, and Squamous Cell Carcinoma: A Spectrum of Disease Progression

R. S Padilla, S Sebastian, Z Jiang, I Nindl and R. Larson    

Abstract:

Objectives  To identify and compare the gene expression profiles of actinic keratosis (AK) and squamous cell carcinoma (SCC) and to further clarify critical genetic alterations in the evolution of SCC from normal sun-damaged human skin.

Design  Observational study.

Setting  University practice.

Patients  Skin biopsy specimens were obtained from 16 patients. The specimens included 14 normal non–sun-exposed skin samples, 14 normal sun-exposed skin samples, 5 AKs, and 15 cutaneous SCCs.

Main Outcome Measures  Gene expression profiles from normal non–sun-exposed skin, normal sun-exposed skin, AKs, and SCCs.

Results  Using a highly astringent shrunken centroid threshold of 6.52 and the prediction analysis of microarrays, we identified 89 unique genes that most likely contribute to the molecular evolution of SCC. Our model was cross-validated using data from a separate study and clearly distinguishes between skin tumors (AK and SCC) and normal skin independent of sun exposure. Genes that were upregulated in AK and SCC were downregulated in normal skin, and genes that were downregulated in AK and SCC were upregulated in normal skin.

Conclusions  The finding of similar differentially expressed genes in AK and SCC confirms that AK is a precursor lesion of SCC and indicates that they are closely related genetically. Clear elucidation of these relationships will be critical to improving therapeutic approaches.

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