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Updated: Aug 14, 2026

CUBIC Protocol Visualizes Protein Expression at Single Cell Resolution in Whole Mount Skin Preparations
Published on: August 4, 2016
Ber-EP4-positive phenotype differentiates actinic keratosis from superficial basal cell carcinoma
W D Tope1, M Nowfar-Rad, D A Kist
1Department of Dermatology, University of Minnesota, Minneapolis, Minnesota 55455-0392, USA. topex001@tc.umn.edu
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.
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