Comprehensive keratin profiling reveals different histopathogenesis of keratocystic odontogenic tumor and orthokeratinized odontogenic cyst.
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.
Aragaki
Tadanobu
T
Section of Oral Pathology, Tokyo Medical and Dental University, Tokyo, Japan.
Michi
Yasuyuki
Y
Katsube
Ken-ichi
K
Uzawa
Narikazu
N
Okada
Norihiko
N
Akashi
Takumi
T
Amagasa
Teruo
T
Yamaguchi
Akira
A
Sakamoto
Kei
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000831:Animals, Newborn; D002280:Basal Cell Carcinoma / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002648:Child; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007573:Jaw Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D007633:Keratins / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D009807:Odontogenic Cysts / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D009808:Odontogenic Tumors / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D055815:Young Adult; D000075746:Zinc Finger Protein Gli2
C082593:GLI2 protein, human; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000075746:Zinc Finger Protein Gli2; C064554:loricrin; D007633:Keratins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases