title: BerEp4, cytokeratin 14, and cytokeratin 17 immunohistochemical staining aid in differentiation of basaloid squamous cell carcinoma from basal cell carcinoma with squamous metaplasia.
abstract: BACKGROUND
  Basaloid squamous cell carcinoma (bSCC) is an uncommon variant of squamous cell carcinoma, which may overlap histologically with basal cell carcinoma with squamous metaplasia (BCCm).
  
  
  OBJECTIVE
  To aid in the differentiation of these neoplasms using immunohistochemical staining because of the worse prognosis associated with bSCC.
  
  
  METHODS
  Using immunohistochemical techniques, we investigated BerEp4, cytokeratin 17 (CK17), and cytokeratin 14 (CK14) protein expression in 25 cases of bSCC (8 cutaneous [32%], 12 aerodigestive tract [48%], and 5 lymph node metastases [20%]) and 43 cases of BCCm (39 cutaneous [91%], and 4 metastases [9%]). An immunoreactivity score was assigned using the percentage of tumor cells staining and the pattern of expression. Interobserver agreement for 2 independent pathologists was assessed using a κ coefficient.
  
  
  RESULTS
  The mean percentage of staining was significantly higher in BCCm, compared with bSCC (BerEp4, P = .006; CK17, P < .001; CK14, P < .001; unpaired t test), with 58% of BCCm cases (25 of 43) displaying diffuse staining for all markers, and nearly all (98%; 42 of 43) displaying diffuse staining for CK17 and CK14. In contrast, no bSCC cases (0%) displayed diffuse staining for all 3 markers, and only 8% (2 of 25) displayed diffuse staining for CK17 and CK14. High interobserver agreement was determined.
  
  
  CONCLUSIONS
  BerEp4 alone is unreliable for differentiation between BCCm and bSCC, and the addition of either CK14 or CK17 will augment the sensitivity and negative predictive value of BerEp4 staining in BCCm and bSCC diagnosis.
authors.affiliation: From the Pathology Service (Drs Linskey, Gimbel, Zukerberg, Duncan, Sadow, and Nazarian); and the Dermatopathology Unit (Drs Linskey, Gimbel, Duncan, and Nazarian), Massachusetts General Hospital, Harvard Medical School, Boston.
authors.forename: Katy R
authors.initials: KR
authors.lastname: Linskey
authors.forename: Devon C
authors.initials: DC
authors.lastname: Gimbel
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Zukerberg
authors.forename: Lyn M
authors.initials: LM
authors.lastname: Duncan
authors.forename: Peter M
authors.initials: PM
authors.lastname: Sadow
authors.forename: Rosalynn M
authors.initials: RM
authors.lastname: Nazarian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002280:Basal Cell Carcinoma / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D002281:Carcinoma, Basosquamous / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D003937:Diagnosis, Differential; D004067:Digestive System Neoplasms / Q000378:metabolism / Q000473:pathology; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053547:Keratin-14 / Q000378:metabolism*; D053537:Keratin-17 / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000951:Antigens, Neoplasm
chemical_list: D014408:Biomarkers, Tumor; D053547:Keratin-14; D053537:Keratin-17; C115012:human epithelial antigen-125; D000951:Antigens, Neoplasm