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COX-2 as a determinant of lower disease-free survival for patients affected by ameloblastoma
Authors:Marco Aurélio Petroni Montezuma  Felipe Paiva Fonseca  Bernar Monteiro Benites  Ciro Dantas Soares  Gleyson Kleber do Amaral-Silva  Oslei Paes de Almeida  Fernando Augusto Soares  Rosana Lima Pagano  Eduardo Rodrigues Fregnani
Affiliation:1. Oral Medicine Department, Sírio-Libanês Hospital, Dona Adma Jafet Street, 115, Bela Vista, São Paulo, SP, 01308-050, Brazil;2. Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Pampulha, Belo Horizonte, MG, Brazil;3. Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Av. Limeira, 901, CEP 13.414-903 Piracicaba, São Paulo, Brazil;4. Department of Pathology, A. C. Camargo Cancer Center, Professor Antônio Prudente Street, 211, ZipCode 01509-010, São Paulo, Brazil;5. Laboratory of Molecular Biology, Sírio-Libanês Hospital, Dona Adma Jafet Street, 115, Bela Vista, São Paulo, SP, 01308-050, Brazil
Abstract:Ameloblastoma is a locally aggressive neoplasm with a poorly understood pathogenesis. Therefore, the aim of this study is to investigate whether COX-2 expression is associated with ameloblastoma microvascular density (MVD) and with tumor aggressiveness. Sixty-three cases of primary ameloblastomas arranged in tissue microarray were submitted to immunohistochemistry against cyclooxigenase-2 (COX-2) and CD34. Clinicopathological parameters regarding sex, age, tumour size, tumour duration, tumour location, treatment, recurrences, radiographic features, vestibular/lingual and basal cortical disruption and follow-up data were obtained from patients’ medical records and correlated with the proteins expression. The results on BRAF-V600E expression were obtained from our previous study and correlated with COX-2 and CD34 expressions. Log-rank univariate analysis and multivariate Cox regression model were done to investigate the prognostic potential of the molecular markers. Twenty-eight cases (44.4%) exhibited cytoplasmic positivity for COX-2, predominantly in the columnar peripheral cells, with a mean MVD of 2.2 vessels/mm2. COX-2 was significantly associated with recurrences (p?<?0.001) and BRAF-V600E expression (p?<?0.001), whereas lower MVD was associated with the use of conservative therapy (p?=?0.004). Using univariate and multivariate analyses, COX-2 was significantly associated with a lower 5-year disease-free survival (DFS) rate (p?<?0.001 and p?=?0.012, respectively), but not with a higher MVD (p?=?0.68). In conclusion, COX-2 expression in ameloblastomas is not associated with MVD, but it is significantly associated with recurrences and with a lower DFS.
Keywords:Ameloblastoma  Odontogenic tumors  COX-2  Cyclooxigenase-2  CD34
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