Identification of Ameloblastin as an Amyloid Precursor Protein of Amyloid-Producing Ameloblastoma in Dogs and Cats

SIMPLE SUMMARY: Amyloid-producing ameloblastoma (APAB) is a rare type of odontogenic tumor found in cats and dogs. This study was conducted to explore this condition further by using proteomic analysis based on mass spectrometry in dogs and cats and identified ameloblastin as an amyloid precursor protein. This study also showed that the N-terminal region of ameloblastin may be involved in the amyloidogenesis. ABSTRACT: Amyloid-producing ameloblastoma (APAB) is characterized by abundant amyloid deposits in ameloblastoma, but the amyloid precursor protein is unknown. To explore this, we conducted histopathologic and proteomic analyses on formalin-fixed and paraffin-embedded samples from five cases of APAB (three dogs and two cats). Histologically, the samples exhibited a proliferation of the odontogenic epithelium, with moderate to severe interstitial amyloid deposits. By using Congo red and polarized light, the amyloid deposits were found to show characteristic birefringence. Amyloid deposits were dissected from tissue sections and analyzed by LC/MS/MS, and high levels of ameloblastin were detected in all tissues. Mass spectrometry also revealed that the N-terminal region of ameloblastin is predominantly present in amyloid deposits. Immunohistochemistry was performed using two anti-ameloblastin (N terminal, middle region) antibodies and showed that amyloid deposits were positive for ameloblastin N terminal but negative for ameloblastin middle region. These results suggest that ameloblastin is the amyloid precursor protein of APABs in dogs and cats, and the N-terminal region may be involved in the amyloidogenesis of ameloblastin.