Immunohistochemical assessment of ATG7, LC3, and p62 in ameloblastomas.
BACKGROUND
To investigate the roles of autophagy in tumorigenesis, cytodifferentiation, and prognosis of odontogenic tumors, we analyzed the immunohistochemical expression of ATG7, LC3, and p62 in odontogenic tissues.


METHODS
Tissue specimens of nine dental follicles and 69 ameloblastomas were immunohistochemically examined with antibodies against ATG7, LC3, and p62.


RESULTS
Immunohistochemical reactivity for ATG7, LC3, and p62 was detected in many odontogenic epithelial cells and several endothelial cells and fibroblasts in dental follicles and ameloblastomas. ATG7 reactivity in ameloblatomas was significantly higher than that in dental follicles. Expression of ATG7, LC3, and p62 was found markedly in neoplastic cells near the basement membrane rather than central polyhedral cells in ameloblastomas. Reactivity for these molecules was significantly higher in unicystic ameloblastomas than in solid ameloblastomas. Granular cells in granular cell ameloblastomas showed obvious reactivity for the autophagy- related molecules, and LC3 reactivity in granular cell ameloblastomas was significantly higher than in other ameloblastoma variations. Recurrent ameloblastomas showed significantly lower reactivity of LC3 and p62 than primary ameloblastomas.


CONCLUSIONS
Expression of ATG7, LC3, and p62 in dental follicles and ameloblastomas suggests that autophagy regulation might be affected by microenvironment alterations during tumorigenesis. The molecular machinery for autophagy is possibly involved in tissue architecture, neoplastic cell differentiation, and prognosis of the benign epithelial odontogenic tumor.
Division of Oral and Maxillofacial Surgery, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry, Sendai, Japan; Division of Oral Pathology, Department of Oral Medicine and Surgery, Tohoku Universtiy Graduate School of Dentistry, Sendai, Japan; Department of Dentistry and Oral Maxillofacial Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan.
Miwa
M
Okada
Mariko
M
Oikawa
Yasuhiro
Y
Miki
Yoshinaka
Y
Shimizu
Seishi
S
Echigo
Tetsu
T
Takahashi
Hiroyuki
H
Kumamoto
D000293:Adolescent; D000328:Adult; D000564:Ameloblastoma / Q000737:chemistry* / Q000473:pathology; D001324:Autoantigens / Q000032:analysis*; D001343:Autophagy / Q000502:physiology; D000071193:Autophagy-Related Protein 7; D001485:Basement Membrane / Q000737:chemistry; D063646:Carcinogenesis / Q000737:chemistry / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D003795:Dental Sac / Q000737:chemistry; D042783:Endothelial Cells / Q000737:chemistry; D004847:Epithelial Cells / Q000737:chemistry; D005260:Female; D005347:Fibroblasts / Q000737:chemistry; D016586:Granular Cell Tumor / Q000737:chemistry / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000737:chemistry / Q000473:pathology; D016601:RNA-Binding Proteins / Q000032:analysis*; D059016:Tumor Microenvironment / Q000502:physiology; D044764:Ubiquitin-Activating Enzymes / Q000032:analysis*
D001324:Autoantigens; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C118585:P62 protein, human; D016601:RNA-Binding Proteins; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes
ameloblastoma; autophagy