Cytokeratin 17, Cytokeratin 19 and BerEP4 expression in basal cell carcinoma and adjacent epithelial structures of the skin
AbstractBackground Cytokeratin (CK) gene expression in the skin reflects the type of epithelium, the differentiation state of epithelial cells and is subjected to striking modulation upon various challenges including carcinogenesis. Objective The aim of the study was to evaluate an immunohistochemical expression status of CK17, CK19 and epithelial cell adhesion molecule EpCAM (BerEP4) in basal cell carcinoma (BCC) and adjacent epithelial structures of the skin. Material and Methods Biopsy samples from 20 cases of BCC were investigated. All were stained for CK17 (clone E3), CK19 (clone RCK108) and EpCAM (clone BerEP4) by immunohisto-chemistry. Results In normal skin, all three markers were constantly positive in the hair follicle components. They were typically negative in the interfollicular epidermis, but the epidermis overlying the tumor and at the edges of tumor mass expressed CK17 in the vast majority of cases. In BCC tissue, the CK17, CK19 and BerEP4 were positive in 100% (20/20), 40% (8/20), and 100% (20/20) of the cases. Conclusion BCC constantly express CK17 and BerEP4 and is variably positive for CK19. Since all three markers are strongly positive in the hair follicle but not in the interfollicular epidermis, the staining pattern of CK17, CK19 and BerEP4 in BCC may provide an evidence to the suggestion that the tumor differentiation is toward follicular germinative epithelium.
Weedon D. Weedon's Skin Pathology. 3th Edition. Churchill Livingstone Elsevier, 2010; p. 248. ISBN 978-0-7020-3485-5
Wang F, Zieman A, Coulombe PA. Skin keratins. Methods Enzymol 2016;568:303-50.
Zhou X, Li G, Wang D, Sun X, Li X. Cytokeratin expression in epidermal stem cells in skin adnexal tumors. Oncol Lett 2019;17:927-932.
Bartoš V, Kullová M. Basal cell carcinoma of the skin: Topographic distribution and clinicopathological differences with regards to the extent of sunlight exposure. J Pakistan Assoc Dermatologists 2016;26:310-317.
Soomro FR, Bajaj DR, Pathan GM, et al. Cutaneous malignant tumors: a profile of ten years at LINAR, Larkana-Pakistan. J Pakistan Assoc Dermatologists 2010;20:133-136.
Dong-Jie S, Xian-Long Q, Zhi L, et al. Review of the clinical features of skin cancer: A study of 1,048 cases from a hospital in West China. J Pakistan Assoc Dermatologists 2007; 17:141-148.
Peterson SC, Eberl M, Vagnozzi AN, Belkadi A, et al. Basal cell carcinoma preferentially arises from stem cells within hair follicle and mechanosensory niches. Cell Stem Cell 2015;16:400-412.
Morgan HJ, Benketah A, Olivero C, et al. Hair follicle differentiation‐specific keratin expression in human basal cell carcinoma. Clin Exp Dermatol 2020;45:417-425.
Beer TW, Shepherd P, Theaker JM. BerEP4 and epithelial membrane antigen aid distinction of basal cell, squamous cell and basosquamous carcinomas of the skin. Histopathology 2000;37:218-223.
Fan YS, Carr RA, Sanders DS, Smith AP, Lazar AJ, Calonje E. Characteristic Ber-EP4 and EMA expression in sebaceoma is immunohistochemically distinct from basal cell carcinoma. Histopathology 2007;51:80-86.
Villada G,Kryvenko ON,Campuzano-Zuluaga G, Kovacs C, Chapman J, Gomez Fernandez C. A limited immunohistochemical panel to distinguish basal cell carcinoma of cutaneous origin from basaloid squamous cell carcinoma of the head and neck. Appl Immunohistochem Mol Morphol 2018;26:126-131.
Krahl D, Sellheyer K. Monoclonal antibody Ber-EP4 reliably discriminates between microcystic adnexal carcinoma and basal cell carcinoma. J Cutan Pathol 2007;34:782-787.
Ishida M, Kushima R, Okabe H. Immunohistochemical demonstration of D2-40 in basal cell carcinomas of the skin. J Cutan Pathol 2008;35:926-930.
Ansai S, Takayama R, Kimura T, Kawana S. Ber-EP4 is a useful marker for follicular germinative cell differentiation of cutaneous epithelial neoplasms. J Dermatol 2012;39:688-692.
Rajabi P, Aboutalebdokht M, Heidarpour M, Asilian A, Rajabi F. Evaluation of diagnostic values of EMA and Ber-Ep4 in distinction between basal cell carcinoma and squamous cell carcinoma of the skin. Iranian J Pathol 2007;2:7-10.
Gamea MM, Elfar NN, Saied EM, Eldeeb S. Study of immunohistochemical expression of cytokeratin 17 in basal cell carcinoma. J Egypt Women's Dermatologic Soc 2016;13:13-16.
Goyal A, Solus JF, Chan MP, et al. Cytokeratin 17 is highly sensitive in discriminating cutaneous lymphadenoma (a distinct trichoblastoma variant) from basal cell carcinoma. J Cutan Pathol 2016;43:422-429.
Zhang X, Yin M, Zhang LJ. Keratin 6, 16 and 17 – critical barrier alarmin molecules in skin wounds and psoriasis. Cells 2019;8:807.
García-de-la-Fuente MR, Santacana M, Valls J, et al. Cytokeratin profile of basal cell carcinomas according to the degree of sun exposure and to the anatomical localization. Am J Dermatopathol 2018;40:342-348.
Heyl J, Mehregan D. Immunolabeling pattern of cytokeratin 19 expression may distinguish sebaceous tumors from basal cell carcinomas. J Cutan Pathol 2008;35:40-45.
Bedir R, Sehitoglu I, Yurdakul C, et al. The importance of cytokeratin 19 expression in the differentiation of basal cell carcinoma and trichoepithelioma. J Clin Diagn Res 2015; 9(1):EC01-EC04.