Odontogenic tumors are rare lesions with unknown etiopathogenesis. Most of them are benign, but local aggressiveness, infiltrative potential, and high recurrence rate characterize some entities. The MAP-kinase pathway activation can represent a primary critical event in odontogenic tumorigenesis. Especially, the BRAF V600E mutation has been involved in 80-90% of ameloblastic lesions, offering a biological rationale for developing new targeted therapies. The study aims to evaluate the BRAF V600E mutation in odontogenic lesions, comparing three different detection methods and focusing on the Sequenom MassARRAY System. 81 surgical samples of odontogenic lesions were subjected to immunohistochemical analysis, Sanger Sequencing, and Matrix-Assisted Laser Desorption/Ionization-Time of Flight mass spectrometry (Sequenom). The BRAF V600E mutation was revealed only in ameloblastoma samples. Moreover, the presence of BRAF V600E was significantly associated with the mandibular site (ρ = 0.627; P value <0.001) and the unicystic histotype (ρ = 0.299, P value <0.001). However, any significant difference of 10-years disease-free survival time was not revealed. Finally, Sequenom showed to be a 100% sensitive and 98.1% specific, suggesting its high-performance diagnostic accuracy. These results suggest the MAP-kinase pathway could contribute to ameloblastic tumorigenesis. Moreover, they could indicate the anatomical specificity of the driving mutations of mandibular ameloblastomas, providing a biological rational for developing new targeted therapies. Finally, the high diagnostic accuracy of Sequenom was confirmed.
Ameloblastoma/pathology* ; Carcinogenesis ; Humans ; Mitogen-Activated Protein Kinases/genetics* ; Mutation ; Odontogenic Tumors/pathology* ; Proto-Oncogene Proteins B-raf/metabolism* ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Clear cell odontogenic carcinoma (CCOC), a rare tumor in the head and neck region, displays comparable properties with other tumors clinically and pathologically. In consequence, an incorrect diagnosis may be established. A 51-year-old male patient who was admitted to the Department of Oral and Maxillofacial Surgery at Pusan National University Dental Hospital was initially diagnosed with ameloblastoma via incisional biopsy. However, the excised mass of the patient was observed to manifest histopathological characteristics of ameloblastic carcinoma. The lesion was ultimately diagnosed as clear cell odontogenic carcinoma by the Department of Oral Pathology of Pusan National Dental University. Therefore, segmental mandibulectomy and bilateral neck dissection were performed, followed by reconstruction with fibula free flap and reconstruction plate. Concomitant chemotherapy radiotherapy was not necessary. The patient has been followed up, and no recurrence has occurred 6 months after surgery.
Ameloblastoma ; Ameloblasts ; Biopsy ; Busan ; Diagnosis ; Diagnostic Errors ; Drug Therapy ; Fibula ; Free Tissue Flaps ; Head ; Humans ; Male ; Mandibular Osteotomy ; Middle Aged ; Neck ; Neck Dissection ; Pathology, Oral ; Radiotherapy ; Recurrence ; Surgery, Oral

Maxillofacial images must be examined to find pathologies not identified during clinical examination. Unicystic ameloblastoma (UA) extending to the mandibular body and ramus was neglected on initial panoramic radiographic examination. After orthodontic therapy, a huge lesion was observed clinically and through imaging exams. After the conservative surgery, no recurrence was observed during five years of follow-up. This case emphasized the need for careful evaluation of patient images focusing on the oral diagnosis before any dental treatment planning, including orthodontic therapy.
Ameloblastoma* ; Delayed Diagnosis* ; Dentistry ; Diagnosis, Oral ; Diagnostic Imaging ; Follow-Up Studies ; Humans ; Mandible* ; Pathology ; Recurrence

Ameloblastoma is a benign odontogenic tumor with an aggressive biological behavior, and the surgical treatment frequently results in failure for the postoperative recurrence. The aim of this article was to investigate whether the proliferative ability and prognosis of ameloblastoma could be evaluated by the radiographic boundary. The ameloblastoma cases treated by the conservative therapy in our hospital between 1981 and 2001 were divided into three groups based on the nature of the radiographic borders of the lesions. The biologic behavior was evaluated by Ki-67 antibody immunohistochemically. Comparisons of prognosis and Ki-67 expression were carried out by statistic methods. There were 24 cases of well-defined edge with sclerosis (group I), 41 cases of well-defined edge without sclerosis (group II) and 32 cases of ill-defined edge (group III). The recurrent rates were 29.2% in group I, 43.9% in group II and 62.5% in group III (P<0.05). The cells in group III expressed the highest Ki-67 level (P<0.05). The radiographic boundary could be used as one of indicators in evaluating the proliferative ability of ameloblastoma and the patient's prognosis, which was consistent with Ki-67 expression.
Adult ; Ameloblastoma ; diagnostic imaging ; pathology ; surgery ; Cell Proliferation ; Chi-Square Distribution ; Female ; Humans ; Ki-67 Antigen ; analysis ; Male ; Mandibular Neoplasms ; diagnostic imaging ; pathology ; surgery ; Middle Aged ; Neoplasm Recurrence, Local ; Observer Variation ; Prognosis ; Radiography, Panoramic ; Retrospective Studies ; Young Adult

Granular cell ameloblastoma is a rare, benign neoplasm of the odontogenic epithelium. A case of massive granular cell ameloblastoma in a 44-year-old Thai female is reported. Histopathological features displayed a follicular type of ameloblastoma with an accumulation of granular cells residing within the tumor follicles. After treatment by partial mandibulectomy, the patient showed a good prognosis without recurrence in a 2-year follow-up. To characterize the granular cells in ameloblastoma, we examined the expression of basement membrane (BM) proteins, including collagen type IV, laminins 1 and 5 and fibronectin using immunohistochemistry. Except for the granular cells, the tumor cells demonstrated a similar expression of BM proteins compared to follicular and plexiform ameloblastomas in our previous study, whereas the granular cells showed strong positivity to laminins 1 and 5 and fibronectin. The increased fibronectin expression in granular cells suggests a possibility of age-related transformation of granular cells in ameloblastoma.
Adult ; Ameloblastoma ; chemistry ; pathology ; Basement Membrane ; chemistry ; Cell Adhesion Molecules ; analysis ; Collagen Type IV ; analysis ; Female ; Fibronectins ; analysis ; Humans ; Keratinocytes ; chemistry ; pathology ; Laminin ; analysis ; Mandibular Neoplasms ; chemistry ; pathology ; Membrane Proteins ; analysis

Ameloblastoma ; pathology ; Bone Neoplasms ; classification ; genetics ; pathology ; Chondromatosis ; pathology ; Chondrosarcoma ; classification ; pathology ; Enchondromatosis ; pathology ; Humans ; Osteosarcoma ; classification ; pathology ; Sarcoma, Ewing ; pathology ; Societies, Medical ; United States ; World Health Organization

Adult ; Ameloblastoma ; pathology ; physiopathology ; Dental Implants, Single-Tooth ; adverse effects ; Female ; Humans ; Whole Body Imaging

OBJECTIVETo study the expression of HOXC13 mRNA in ameloblastoma (AB), and to investigate its biological significance.

METHODSHOXC13 mRNA was examined in 47 cases of AB (primary AB 29 cases, recurrent AB 14 cases, malignant AB 4 cases). 2 cases of fibrous dysplasia of bone, 10 cases of keratocystic odontogenic tumor (KCOT) and 7 cases of normal oral mucosa were selected as control.

RESULTSThe positive rates of HOXC13 mRNA in AB, KCOT, and normal oral mucosa were 97.9% (46/47), 7/10 and 3/7, respectively. There was a significant difference among AB, OKC and normal mucosa (chi(2) = 21.665, P = 0.001). For HOXC13, the keratinizing cells and granulizing cells in AB were negative, some fibroblasts were positive, 2 cases of fibrous dysplasia of bone were positive.

CONCLUSIONSHOXC13 was highly expressed in AB. The expression of HOXC13 mRNA in AB had heterogeneity, which could improve the epithelial proliferation, and its loss may lead to the cornification and degeneration of epithelial cells.

Adolescent ; Adult ; Ameloblastoma ; genetics ; metabolism ; pathology ; Female ; Gene Expression ; Genes, Homeobox ; Homeodomain Proteins ; metabolism ; Humans ; Male ; Middle Aged ; Mouth Mucosa ; metabolism ; Odontogenic Tumors ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Young Adult

OBJECTIVETo investigate the expression of cyclin E mRNA, p21(WAF1) mRNA and p27(KIP1) protein in human ameloblastoma (AB), and to explore the clinical and biological characteristics of AB.

METHODSThe expression of cyclin E mRNA, p21(WAF1) mRNA and p27(KIP1) protein in 54 cases of human AB were detected by in situ hybridization or immunohistochemistry (SP method).

RESULTSThe positive expression rate of cyclin E mRNA in the cytoplasm or cell nucleus of AB was 66.7% (36/54). The expression of cyclin E mRNA increased with AB recurrence and malignant transformation, and the difference of expression among primary AB, recurrent AB, and malignant AB, was statistically significant. The positive expression ratio of cyclin E mRNA in OKC was 50.0% (8/16). The p21(WAF1) mRNA expression in the cytoplasm or cell nucleus of AB decreased, and the positive ratio was 22.6% (12/54) in AB, 37.5% (6/16) in OKC, respectively. The p27(KIP1) protein expression in the cell nucleus of AB was positive in a small number of cases, and the positive rate was 16.7% (9/54) in AB, 6.3% (1/16) in OKC, respectively.

CONCLUSIONSThe genesis and invasion of AB is associated with the cell proliferation and differentiation, and regulated by the higher expression of cyclin E and the lower expression of p21(WAF1) and p27(KIP1).

Adolescent ; Adult ; Aged ; Ameloblastoma ; metabolism ; pathology ; Child ; Cyclin E ; genetics ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; metabolism ; Cyclin-Dependent Kinase Inhibitor p27 ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; Jaw Neoplasms ; metabolism ; pathology ; Middle Aged ; Oncogene Proteins ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Young Adult

OBJECTIVETo investigate the expression of pRb and E2F-1, and the association between their expression and the activity of telomerase (hTERT) or cyclin E in human ameloblastoma (AB), and to explore the clinical biological characteristics of AB.

METHODSThe expressions of pRb, E2F-1, cyclin E and hTERT mRNA in human AB were detected by in situ hybridization or immunohistochemistry (SP method).

RESULTSThe positive expression ratio of pRb in the cell nucleus of AB was 20.4% (11/54). The positive ratio of E2F-1, cyclin E and hTERT mRNA was 92.6% (50/54), 66.7% (36/54) and 94.4% (51/54), respectively. With AB recurrence and malignant transformation, the expression of hTERT, E2F-1, cyclin E was up-regulated. hTERT and cyclin E or E2F-1 mRNA had high positive relation (Spearsman'r(s) = 1.000, P = 0.0001).

CONCLUSIONSThe regulatory pathway of Rb/E2F-1 is associated with the cell proliferation and in differentiation of AB. The activity or release of telomerase may be related to the lower expression of Rb and higher expression of E2F-1, and is up-regulated in G(1) late phase by cyclin E.

Adolescent ; Adult ; Aged ; Ameloblastoma ; metabolism ; pathology ; Child ; Cyclin E ; biosynthesis ; E2F1 Transcription Factor ; biosynthesis ; Female ; Humans ; Jaw Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; RNA, Messenger ; biosynthesis ; Retinoblastoma Protein ; biosynthesis ; Telomerase ; genetics ; metabolism