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Comprehensive keratin profiling reveals different histopathogenesis of keratocystic odontogenic tumor and orthokeratinized odontogenic cyst.

Abstract
Keratocystic odontogenic tumor is a cystic lesion that behaves more aggressively than other jaw cysts. One of its characteristic histologic features is a parakeratinized uniform layer of lining epithelium. A jaw cyst lined with orthokeratinized epithelium is called an orthokeratinized odontogenic cyst. These keratinized jaw cysts are thought to be separate entities, although their histopathogenesis has not been fully assessed. To better understand these lesions, we performed comprehensive immunohistochemical profiling of the keratin expression of each. Orthokeratinized odontogenic cysts expressed keratin 1, keratin 2, keratin 10, and loricrin, suggesting differentiation toward normal epidermis. Keratocystic odontogenic tumors expressed keratin 4, keratin 13, keratin 17, and keratin 19, which is a unique expression pattern reminiscent of a mucosal squamous epithelium and an epithelial appendage. In neonatal rat tooth germ, cells strongly positive for keratin 17 and keratin 19 were observed, specifically in the dental lamina, implying the origin of keratocystic odontogenic tumor. GLI2, a downstream effector of hedgehog signaling, was significantly expressed in keratocystic odontogenic tumor and basal cell carcinoma, accompanied with robust expression of keratin 17, mammalian target of rapamycin, and BCL2. The expression of these GLI2- or keratin 17-related factors was not significantly observed in orthokeratinized odontogenic cysts. These findings provide evidence to support the viewpoint that keratocystic odontogenic tumor and orthokeratinized odontogenic cyst are separate entities, and furthermore suggest their characteristic histology, pathogenesis, and biological behaviors.
AuthorsTadanobu Aragaki, Yasuyuki Michi, Ken-ichi Katsube, Narikazu Uzawa, Norihiko Okada, Takumi Akashi, Teruo Amagasa, Akira Yamaguchi, Kei Sakamoto
JournalHuman pathology (Hum Pathol) Vol. 41 Issue 12 Pg. 1718-25 (Dec 2010) ISSN: 1532-8392 [Electronic] United States
PMID20801488 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier Inc. All rights reserved.
Chemical References
  • GLI2 protein, human
  • Kruppel-Like Transcription Factors
  • Membrane Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • loricrin
  • Keratins
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
Topics
  • Adolescent
  • Adult
  • Aged
  • Animals
  • Animals, Newborn
  • Carcinoma, Basal Cell (metabolism, pathology, surgery)
  • Child
  • Epithelial Cells (metabolism, pathology)
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Jaw Neoplasms (metabolism, pathology, surgery)
  • Keratins (metabolism)
  • Kruppel-Like Transcription Factors (metabolism)
  • Male
  • Membrane Proteins (metabolism)
  • Middle Aged
  • Nuclear Proteins (metabolism)
  • Odontogenic Cysts (metabolism, pathology, surgery)
  • Odontogenic Tumors (metabolism, pathology, surgery)
  • Proto-Oncogene Proteins c-bcl-2 (metabolism)
  • Rats
  • TOR Serine-Threonine Kinases (metabolism)
  • Young Adult

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