Ber-EP4-Positive Phenotype Differentiates Actinic Keratosis from Superficial Basal Cell Carcinoma


  • W.D. Tope, MPhil, MD, M. Nowfar-Rad, MD, and D.A. Kist, BA, HTL (ASCP) have indicated no significant interest with commercial supporters.

Address correspondence and reprint requests to: Whitney D. Tope, MD, University of Minnesota, Box 98FUMC, Delaware St. SE, Minneapolis, MN 55455-0392, or e-mail:


Background. Well-defined histopathologic criteria exist to distinguish actinic keratosis (AK) from superficial basal cell carcinoma (BCC). A similar morphology of downwardly budding dysplastic keratinocytes may occur in both entities, creating potential for errors in diagnosis. A marker that could reliably distinguish these two lesions would overcome this difficulty in diagnosis.

Objective. To investigate whether Ber-EP4 staining is useful in distinguishing AK from superficial BCC, and to determine whether AK exhibits a cellular phenotype that is more consistent with BCC or squamous cell carcinoma (SCC).

Methods. We subjected tissue sections from superficial BCC, AK, and squamous intraepithelial neoplasia (SIN) demonstrating epidermal budding to immunohistochemical staining with monoclonal antibody Ber-EP4.

Results. Abnormal keratinocytes in all specimens of superficial BCC (5 of 5) were Ber-EP4 positive; all AK (10 of 10) and SIN (8 of 8) were Ber-EP4 negative.

Conclusion. Ber-EP4 staining reliably distinguishes AK from superficial BCC. The lack of Ber-EP4 staining of AK supports the currently accepted pathogenetic dogma that SIN and SCC arise from AK, but BCC does not.