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PathologyIHCN/A (pathology)

BerEP4 immunohistochemistry

Ber-EP4; EpCAM; CD326; epithelial cell adhesion molecule

BerEP4 is a monoclonal antibody directed against EpCAM (epithelial cell adhesion molecule, CD326). It is a widely used IHC marker in dermatopathology for distinguishing basal cell carcinoma (which shows strong, diffuse membranous staining in > 95% of cases) from cutaneous squamous cell carcinoma (typically BerEP4-negative or only weakly positive) and from many adnexal carcinomas and metastatic carcinomas. It is particularly helpful where small biopsy fragments or basaloid morphology make distinction by H&E alone unreliable — clinically relevant when planning Mohs vs WLE or distinguishing BCC from MAC, trichoblastoma, basaloid SCC, sebaceous carcinoma and metastasis.

CurrentLast reviewed 15 May 2026

BerEP4-positive lesions

  • Basal cell carcinoma — > 95% strong diffuse membranous staining in all subtypes (nodular, superficial, infiltrative, micronodular, basosquamous, morphoeic).
  • Trichoblastoma / trichoepithelioma — also positive (BerEP4 alone cannot reliably distinguish from BCC; CD10 stromal pattern, PHLDA1, CK20 add value).
  • Many metastatic carcinomas (breast, colorectal, lung).
  • Some adnexal carcinomas (variable).

BerEP4-negative lesions

  • Cutaneous squamous cell carcinoma — typically negative or only patchy weak staining (< 10% strongly positive).
  • Sebaceous carcinoma — usually negative; EMA / adipophilin / androgen receptor establish sebaceous differentiation.
  • Microcystic adnexal carcinoma — variable; often negative or patchy.
  • Melanoma — negative; melanocyte markers establish lineage.
  • Eccrine porocarcinoma — variable; often negative.
  • Atypical fibroxanthoma / pleomorphic dermal sarcoma — negative (mesenchymal).

Clinical context — BCC vs cSCC

  • Basaloid SCC vs BCC — small biopsy fragments may not show diagnostic features; BerEP4-positive favours BCC, BerEP4-negative + p63-strong + EMA-positive favours SCC.
  • Mohs vs WLE planning — BerEP4 confirmation supports appropriate management of basaloid lesions.
  • Micronodular / infiltrative BCC margin assessment — BerEP4 helps identify tumour at deep / peripheral margins where H&E features are subtle.
  • BCC in chronically sun-damaged skin — distinguishes BCC nests from solar elastotic / basaloid follicular hamartoma where ambiguous.
  • Naevus sebaceus secondary tumour — BerEP4 helps distinguish BCC from trichoblastoma (both common in NS) when combined with other markers (CD10 stromal, PHLDA1).

Pitfalls

  • Trichoblastoma is BerEP4-positive — cannot distinguish from BCC by BerEP4 alone.
  • Some basaloid SCCs show focal BerEP4 positivity — interpret with morphology and other markers.
  • Sebaceous carcinoma can have BerEP4-positive basaloid cells in some cases — adipophilin / EMA / androgen receptor needed.
  • Metastatic carcinoma at a cutaneous site may be BerEP4-positive — clinical context (history of cancer, distribution) is essential.
  • BerEP4 is not a substitute for thorough morphological assessment; use as adjunct.

References

  1. Beer TW, Drury P, Heenan PJ. Atypical fibroxanthoma — a histological and immunohistochemical review of 171 cases. Am J Dermatopathol; 2010.
  2. Sellheyer K. Basal cell (trichoblastic) carcinoma — common diagnostic pitfalls. J Am Acad Dermatol; 2007.
  3. WHO Classification of Tumours Editorial Board. Skin Tumours, WHO Classification of Tumours, 5th ed., vol. 12. Lyon: IARC; 2025.

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