Study On Mutation Of BRAF V600E Gene In Ameloblastoma,Ameloblastic Fibroma And Keratocystic Odontogenic Tumor

Objective:To investigate the prevalence of the BRAF V600E mutation in ameloblastoma(AM),ameloblastic fibroma(AF)and keratocystic odontogenic tumor(KCOT)of the jaws in a Chinese population,further analyzed the relationship between the BRAF mutation and clinical characteristic to provide a new reference to the study of these diseases'molecular pathology and new molecular targeted therapies.And on this basis we investigate the clinical features,pathologic manifestations,and biologic behaviors of a variant of ameloblastoma with basal cell features(AM-BC).Methods:DNA was extracted from 160 AM,16 AF and 33 KCOT samples.All the samples were evaluated for BRAF mutation at exon 15 via PCR and Sanger sequencing.The clinical characteristics of BRAF V600E mutant-type variant and wild-type variant were compared in AM,AF and KCOT patients.The histological type,age,sex,lesion location,symptoms,surgical procedures and recurrence were reviewed and statistically analyzed.Following retrospective review of the clinical and histologic and immunohistochemical features of six cases of AM-BC,and discussed the relationship between BRAF mutation and the biologic behaviors,prognoses,pathogenesis,and clinical relevance of AM-BC.Results:155 out of 160 AM samples(96.9%)and all the 16 AF samples(100%)harbored the p.V600E hot spot mutation,whereas none of the 33 KCOT samples carried this mutation(0%).The mutation was not related to histological type,age,sex,and lesion location in AM and AF patients.The six cases of AM-BC involved four women and two men,aged 22-82 years.Four lesions occurred in the maxilla and two in the mandible.Two patients had BRAF gene mutations(33.3%).Histologically,the basal cells tended to be arranged as unequally-sized follicles,strands,or cords of odontogenic epithelium in the connective tissue stroma.Little or no stellate reticulum was present in the central portion of the nest.Expression of CKs was consistent with other histological variants of ameloblastoma(AM),but AM-BC had significantly higher p53 and Ki-67(P<0.05)labeling indices than other histological variants of AM.Conclusion:Our data confirmed a positive correlation between the BRAF V600E mutation and AM,AF in a Chinese population.The mutation is not related to the histological type,age,sex,and lesion location in AM and AF.The absence of BRAF V600E mutation in KCOT patients indicates that this gene may not be involved in the pathogenesis of this disease.AM-BC is a very rare variant of AM.The clinical symptoms of AM-BC were not significantly different from those of other types of ameloblastomas.It has a unique manifestation in histologic appearance.The origin of AM-BC was the same as that of other types of ameloblastomas,and all of them came from odontogenic epithelial tissues.AM-BC has stronger proliferation and invasion ability and lower BRAF gene mutation rate,which should be treated differently from other types of ameloblastomas in clinical treatment.