title: The changes in the expression levels of follicular markers in keratoacanthoma depend on the stage: keratoacanthoma is a follicular neoplasm exhibiting infundibular/isthmic differentiation without expression of CK15.
abstract: BACKGROUND
  Although the precise etiology of keratoacanthoma (KA) is unknown, KA is generally assumed to differentiate toward hair follicles based on previous studies of experimental carcinogenesis.
  
  
  METHODS
  We performed a comprehensive immunohistochemical study of various follicular markers in all stages of KA. A total of 67 tumors, including 16 early or proliferative stage lesions, 43 well-developed stage lesions, five regressing stage lesions and three regressed stage lesions, were subjected to the analysis.
  
  
  RESULTS
  CK15 (clone C8/144B), CK19 and CD34 were not expressed at any stage. CK1, CK10, CK16, CK17, CK15 (clone LHK15) and calretinin showed dynamic changes in their expression in KA depending on the stage.
  
  
  CONCLUSIONS
  KA is a follicular neoplasm with infundibular/isthmic (upper segmental region of hair follicles) differentiation. It is considered that early or proliferative stage tumors show keratin-filled invaginations with infundibular differentiation and gradual isthmic differentiation. Well-developed examples of KA generally show isthmic differentiation in the whole lesions. The regressed stage KAs lose the features of this type of follicular differentiation and show epidermal characteristics. No expression of CK15 (clone C8/144B) was observed in KAs, although this finding is insufficient to completely rule out the correlation between the regression of KA and the hair follicle cycle.
authors.affiliation: Division of Dermatology, Department of Internal Medicine, Saga University, Saga, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Misago
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Takai
authors.forename: Shuji
authors.initials: S
authors.lastname: Toda
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Narisawa
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002454:Cell Differentiation; D018859:Hair Follicle / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D053569:Keratin-15 / Q000096:biosynthesis; D007636:Keratoacanthoma / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D053569:Keratin-15
keywords: bulge stem cells; calretinin; cytokeratin; follicular differentiation; keratoacanthoma