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Nuclear Morphometry and Molecular Biomarkers of Actinic Keratosis, Sun-Damaged, and Nonexposed Skin

¹ The Chao Family Comprehensive Cancer Center; Departments of ² Pathology and ³ Dermatology; and Divisions of ⁴ Epidemiology and ⁵ Hematology-Oncology of the Department of Medicine, the University of California Irvine, Irvine, California

Requests for reprints: Philip M. Carpenter, Department of Pathology, Irvine Medical Center, University of California, Building 10, Route 40, Room 104, 101 The City Drive South, Orange, CA 92868, USA. Phone: 714-456-6141; Fax: 714-456-5873.E-mail: pmcarpen{at}uci.edu

Computer-assisted image analysis is useful for quantifying the histologic and molecular changes of sun-induced squamous cell carcinoma progression. We used the CAS 200 image analysis system to measure nuclear morphometric parameters, p53 expression, and proliferation markers in actinic keratosis (AK), sun-exposed, and normal skin in 51 patients. Nuclear morphometry revealed significant increases in nuclear absorbance, irregularity of nuclear shape, and nuclear size in AK compared with normal and sun-damaged skin. These parameters showed significantly greater variability in AK nuclei. Argyrophyllic nucleolar organizer area and number were also significantly greater in AK compared with sun-damaged skin and normal skin. Ki67 and p53 expressions were both increased in sun-damaged skin relative to normal and greater still in AK. These data are evidence that sun damage induces proliferation and p53 abnormalities before the appearance of nuclear abnormalities and their associated DNA instability. Following these changes during a skin cancer chemopreventative trial can then help assess the efficacy of the agent and help determine where in the progression of neoplastic changes it exerts its biological effects.

Key Words: Actinic Keratosis • Image Analysis • Chemoprevention • Nuclear Morphometry • p53 • Proliferation

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