Letter to the Editor The importance of follicular stem cells in veterinary medicine in the context of skin tumours We read with special interest the article ‘Canine hair-folli- cle keratinocytes enriched with bulge cells have the highly proliferative characteristic of stem cells’ by Kobay- ashi et al. 1 published in Veterinary Dermatology. The study showed encouraging results, suggesting the exis- tence of an epithelial stem cell compartment, based on immunohistochemistry, culture, microdissection and flow cytometry analysis. Currently, there is increasing interest in the follicular stem cell compartment, because this cell type is charac- terized by extensive growth and differentiation capacity, which may be applied to the development of new strate- gies in regenerative medicine and gene therapy. 2,3 Although occasionally forgotten, one of the applications of this new field of research resides in the better under- standing of adnexal tumour differentiation and further elu- cidation of the histogenesis of a given tumour. 3 Despite interest in this approach, there are few studies describing the use of immunohistochemical markers to localize stem cell candidates in animal neoplasms. 1,2,4,5 Among these markers, CK15, CD34 and nestin are the only proteins that have been used in stem cell identifica- tion in veterinary medicine. 1,2,4,5 Immunolabelling for cytokeratin 15 (CK15) has been reported in sweat gland neoplasms, basal cell carcinomas, trichilemmomas and squamous cell carcinomas. 6–8 In contrast, pilomatricomas and Merkel cell carcinoma yielded negative results, 9–11 and in a clear cell adnexal carcinoma of a dog only 1% of neoplastic cells, which are supposed to have follicular origin, were positive for CK15. 12 The protein CD34, a hallmark of haematopoietic stem cells, recently demonstrated its value as a follicular stem cell marker in murine bulge keratinocytes. 13 The presence of mRNA and CD34 glycoprotein was demonstrated in the isthmic region of canine hair follicles by in situ hybrid- ization and immunohistochemistry. 7 These findings sup- port the hypothesis that dogs have a bulge-like region, similar to humans and mice. 5 Despite this, no studies regarding CD34 expression in cutaneous neoplasms from animals have been made to date. Finally, the neuroepithelial stem cell protein nestin, which was initially identified as a marker for neuronal pro- genitor cells, 3 was identified in the middle region of hair follicles in healthy dogs. 2 Nestin expression was variable in sweat gland tumours, 6 squamous cell carcinomas, 8 peritumoural stroma of basal cell carcinomas, trichoblas- tomas and trichoepitheliomas, 3 but was negative in Merkel cell carcinomas. 8 Expression patterns of other stem cell markers, such as B-lymphocyte-induced maturation protein-1, p63, CK19, CD200 and pleckstrin homology-like domain family A member 1, 3 need to be investigated in veterinary medi- cine, both in normal skin and in neoplastic skin disorders. Fabrizio Grandi*†, Bruna F. Firmo†, Marcia M. Colodel†, Rafael M. Rocha‡, Juliana Werner§ and Noeme S. Rocha*† *Department of Pathology, Botucatu Medical School, Universidade Estadual Paulista – UNESP, Botucatu, Sa ˜ o Paulo, Brazil †Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, Universidade Estadual Paulista – UNESP, Botucatu, Sa ˜ o Paulo, Brazil ‡Department of Pathology, A. C. Camargo Cancer Hospital, Sa ˜ o Paulo, Brazil §Werner & Werner Veterinary Pathology Diagnostic Centre, Parana ´ , Brazil References 1. Kobayashi T, Shimizu A, Nishifuji K et al. Canine hair-follicle keratinocytes enriched for bulge cells have the highly prolifera- tive characteristic of stem cells. Veterinary Dermatology 2009; 20: 338–46. 2. Mercati F, Pascucci L, Gargiulo AM et al. Immunohistochemical evaluation of intermediate filament nestin in dog hair follicles. Histology and Histopathology 2008; 23: 1035–41. 3. Sellheyer K. Stem cell markers can help identify adnexal tumor differentiation when evaluated in the context of morphology: methodology matters. Journal of Cutaneous Pathology 2011; 38: 460–74. 4. Kobayashi T, Iwasaki T, Amagai M et al. Canine follicle stem cell candidates reside in the bulge and share characteristic features with human bulge cells. Journal of Investigative Dermatology 2010; 130: 1988–95. 5. Pascucci L, Mercati F, Gargiulo AM et al. CD34 glycoprotein identifies putative stem cells located in the isthmic region of canine hair follicles. Veterinary Dermatology 2006; 17: 244– 51. 6. Mahalingam M, Srivastava A, Hoang MP. Expression of stem- cell markers (cytokeratin 15 and nestin) in primary adnexal neoplasms—clues to etiopathogenesis. American Journal of Dermatopathology 2010; 32: 774–9. 7. Kanoh M, Amoh Y, Sato Y et al. Expression of the hair stem cell- specific marker nestin in epidermal and follicular tumors. Euro- pean Journal of Dermatology 2008; 18: 518–23. 8. Abbas O, Bhawan J. Expression of stem cell markers nestin and cytokeratin 15 and 19 in cutaneous malignancies. Journal of the European Academy of Dermatology and Venereology 2011; 25: 311–6. 9. Jih DM, Lyle S, Elenitsas R et al. Cytokeratin 15 expression in trichoepitheliomas and a subset of basal cell carcinomas suggests they originate from hair follicle stem cells. Journal of Cutaneous Pathology 1999; 26: 113–8. Correspondence: Fabrizio Grandi, Laboratory of Investigative and Comparative Pathology, Veterinary Pathology Service, School of Veterinary Medicine and Animal Science, Universidade Estadual Paulista – UNESP, Distrito de Rubia ˜ o Ju ´ nior, s / n, 18618-970 Botucatu, Sa ˜ o Paulo, Brazil. E-mail: fgrandivet@gmail.com ª 2011 The Authors. Veterinary Dermatology ª 2011 ESVD and ACVD, Veterinary Dermatology, 23, 81–83. 81 DOI: 10.1111/j.1365-3164.2011.01010.x