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Diagnosing Xeroderma Pigmentosum Group C by Immunohistochemistry

de Feraudy, Sébastien MD*; Boubakour-Azzouz, Imenne PhD*; Fraitag, Sylvie MD; Berneburg, Mark MD; Chan, Loretta BS§; Chew, Kevin BS§; Clericuzio, Carol L MD; Cunningham, Bari MD; Tope, Whitney D MPhil, MD*; Cleaver, James E PhD*

The American Journal of Dermatopathology: April 2010 - Volume 32 - Issue 2 - p 109-117
doi: 10.1097/DAD.0b013e3181af0a5e
Original Study

Xeroderma pigmentosum (XP) is a group of rare inherited human neurocutaneous diseases, and the group C (XPC) is the major group of patients with XP in Europe, North America, and South America. Current molecular diagnostic methods for XP require specialized, expensive, and time-consuming UV sensitivity and DNA repair assays followed by gene sequencing. To determine whether immunohistochemistry (IHC) would be a robust alternative method to diagnose patients with XPC, we stained sections of paraffin-embedded skin biopsies for XPC by IHC, using 69 archived blocks from confirmed or clinically suspect patients with XPA, XPC, XPD, XPE, and without XP. We found that XPC expression was strong in all skin biopsies from patients without (14 of 14) and other patients with XP (4 of 4), whereas XPC expression was lost in all biopsies from confirmed XPC patients (29 of 29). Patches of strong XPC signal could be detected in sun-damaged skin, squamous and basal cell carcinomas from patients with XPC that colocalized with strong expression of p53 and Ki-67. Patients with XPC can therefore be diagnosed by IHC from paraffin-embedded skin biopsies from regions of skin that are without sun damage or sun-induced tumors. IHC is therefore a robust alternative method to diagnose patients with XPC. This fast and inexpensive method should increase the options for the diagnosis of patients with XPC from paraffin-embedded skin biopsies and could be developed for other complementation groups.

From the *Department of Dermatology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; †Service d'Anatomie et de Cytologie Pathologiques, Groupe d'Etude des Maladies Génétiques à Expression Cutanée, Hôpital Necker-Enfants Malades, Paris, France; ‡Department of Dermatology, Phototherapy, Lasermedicine, PDT, Eberhard Karls University, Tuebingen, Germany; §Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; ¶Division of Genetics/Dysmorphology, Department of Pediatrics, University of New Mexico, Albuquerque, NM; and ‖University of California San Diego, Comprehensive Dermatology Group, 477 N El Camino Real Suite C204, Encinitas, CA. Kevin Chew is now with the Genomic Health, Inc, 301 Penobscot Drive, Redwood City, CA 94063 and Whitney D. Tope is now in 1120 Wayzata Boulevard W, Wayzata, MN 55391-952.

Supported by grants from the National Institutes of Neurological Disorders and Stroke grant 1R01NS052781 (J.E.C.) and a program project grant from NIAMS P01 AR050440 (Principal Investigator: Balmain).

The authors have no conflict of interest.

Technical assistance for pictures was provided by Dr. Ei-Chang Jung, MD.

Sample preparations were carried out by the University of California, San Francisco, Cancer Center Tissue Core.

Reprints: James E. Cleaver, PhD, Department of Dermatology, Auerback Melanoma Laboratory, Room N431, Box 0808, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143-0808 (e-mail: jcleaver@cc.ucsf.edu).

© 2010 Lippincott Williams & Wilkins, Inc.