Histopathological Remodeling and Reduced Hypoxia-Related Marker Expression Following Marsupialization of Ameloblastoma: A Paired Analysis

Background: Marsupialization is widely used as a jaw-preserving treatment for large cystic ameloblastomas and is generally believed to reduce tumor volume through decompression. However, the biological mechanisms underlying tumor regression remain poorly understood. This study aimed to investigate the histopathological and hypoxia-related molecular changes in ameloblastoma before and after marsupialization using paired specimens from the same patients. Methods: This retrospective paired study included 13 patients with ameloblastoma who underwent marsupialization (median duration, 3 months; range, 1–12 months) followed by enucleation with peripheral ostectomy. Histopathological and immunohistochemical changes were compared between paired pre- and post-marsupialization specimens obtained from the same patients. Expression of the hypoxia-related molecules HIF-1α, carbonic anhydrase IX (CA IX), glucose transporter 1 (GLUT1), vascular endothelial growth factor (VEGF), and the proliferation marker Ki-67 was evaluated. Results: Marsupialization was associated with characteristic histopathological alterations, including increased squamous metaplasia, reduced stellate reticulum-like morphology, and a shift from myxoid to fibrous stromal patterns. Nuclear HIF-1α expression decreased significantly after marsupialization, accompanied by coordinated reductions in CA IX, GLUT1, VEGF, and the Ki-67 labeling index. These findings were consistent with coordinated attenuation of hypoxia-associated signaling together with reduced Ki-67 labeling. Conclusions: This study provides within-patient pathological evidence of histopathological remodeling and reduced hypoxia-related marker expression following marsupialization in ameloblastoma. These findings suggest that the tissue response to marsupialization may involve attenuation of hypoxia-associated signaling.