Ana Lúcia Amaral Eisenberg

Assessment of BRAFV600E and SMOF412E mutations in epithelial odontogenic tumours

The classification of ameloblastoma in multicystic or unicystic variants is associated with its clinical behaviour. Recently, BRAF and SMO mutations have been reported in ameloblastomas. However, it is not clear if such mutations are shared by the multi- and unicystic variants of ameloblastoma or by odontogenic carcinomas. We assessed BRAFV600E and SMOF412E in multicystic, unicystic and desmoplastic ameloblastomas. In addition, we investigated whether the BRAFV600E mutation occurs in odontogenic carcinomas. A total of 28 formalin-fixed paraffin-embedded samples, comprising 17 ameloblastomas and 11 odontogenic carcinomas, were included. The BRAFV600E mutation was assessed by real-time PCR with a specific TaqMan probe and confirmed by Sanger sequencing. The SMOF412E mutation was assessed by Sanger sequencing. Fourteen out of 17 (82xa0%) ameloblastomas showed the BRAFV600E mutation, specifically, 5/6 (83xa0%) unicystic, 7/9 (78xa0%) multicystic and 2/2 desmoplastic ameloblastomas. BRAFV600E mutation was detected in 4/11 (36xa0%) malignant tumours, specifically, 3/8 (38xa0%) ameloblastic carcinomas and 1/1 clear cell odontogenic carcinoma, while the two ghost cell odontogenic carcinomas did not harbour this mutation. The SMOF412E mutation was not detected in ameloblastoma. The BRAFV600E-activating mutation is a common event in ameloblastomas, occurring regardless of site or histological type. This mutation is also detected in odontogenic carcinomas. SMO somatic mutation is a secondary genetic event in the ameloblastoma pathogenesis. Our findings support the possibility for personalised, molecular-targeted therapy for ameloblastomas and odontogenic carcinomas harbouring the BRAFV600E mutation.

Assessment of angiogenesis by CD105 antigen in epithelial salivary gland neoplasms with diverse metastatic behavior

BackgroundInformation on the biology of metastasis development in salivary gland tumors is scarce. Since angiogenesis seems associated with this phenomenon in other tumors, we sought to compare salivary gland tumors with diverse metastatic behavior in order to improve the knowledge and management of these lesions.MethodsSamples from the most important salivary gland tumors were segregated according to its metastatic behavior and submitted to routine immunohistochemistry to identify vessels positive for CD105 expression. Frequency of positive cases and intratumoral microvessel density (IMD) was compared among the group of lesions.ResultsCD105 positive vessels were absent in normal salivary gland tissue, were rare in pleomorphic adenomas and adenoid cystic carcinomas (ACC), more common in polymorphous low-grade adenocarcinomas and highest in mucoepidermoid carcinomas. Only ACC with such feature were metastatic. IMD was higher in malignant rather than benign tumors.ConclusionImmunostaining of CD105 in salivary gland tumors implies participation of angiogenesis in the development of malignant lesions, as well as some role for myoepithelial cells in the control of new vessel formation. In addition, suggest that ACC with positive CD105 vessels are at higher risk for metastasis.

Clear cell odontogenic carcinoma: report of 7 new cases and systematic review of the current knowledge.

OBJECTIVEnThe goal of this study is to describe 7 cases of clear cell odontogenic carcinoma among a Brazilian population and compare these data with a systematic review of the English-language literature.nnnSTUDY DESIGNnDescriptive statististics were used to compare the clinicopathologic data gathered retrospectively with those compiled from a review. Tumor sections were immunostained for Ki-67, p16, p53, and cytokeratins (CKs) 7, 8, 14, 18, and 19. Log-rank tests were performed for survival analysis.nnnRESULTSnMost cases occurred in the posterior mandible (5/7, 71.4%), and recurrence was diagnosed in all treated patients. Metastatic disease occurred in 2 patients (28.6%). Tumors were focally positive for CKs 7, 8, 14, and 18 and diffusely positive for CK19, p53, and p16. The mean number of Ki-67-positive cells was 35.2 cells/high-power field. Our systematic review provided evidence that tumor size (Pxa0= .046), histologic pattern (Pxa0= .034), regional metastasis (Pxa0= .001), distant metastasis (Pxa0= .001), and local recurrence (Pxa0= .05) were of significant prognostic value.nnnCONCLUSIONSnThis study has contributed to improved characterization of clear cell odontogenic carcinoma, which is an aggressive odontogenic malignant neoplasm diagnosed mainly in the posterior mandible of middle-aged women and typically at an advanced stage. Radical surgical procedures remain the gold standard treatment.

Vascular endothelial growth factor and thymidine phosphorylase expression in salivary gland tumors with distinct metastatic behavior

BACKGROUNDnMetastasis of salivary gland tumors has a negative impact on survival. Angiogenesis and its factors are potential markers for predicting metastasis in different malignant tumors, but this is not the case for salivary gland tumors.nnnMETHODSnSalivary gland tumors of distinct biologic behavior were analyzed according to the semiquantitative immunoexpression of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP).nnnRESULTSnVascular endothelial growth factor expression was predominantly weak in benign tumors. Weak TP expression was observed in 100% cases of benign tumors and in 74.3% of primary malignant tumors. High VEGF and TP expression levels were significantly associated with primary malignant tumors but not with primary non-metastasizing and primary metastasizing malignant tumors or with subtypes of malignant tumors.nnnCONCLUSIONSnVascular endothelial growth factor and TP expression levels discriminate benign and malignant tumors but cannot predict metastasis from non-metastasizing tumors.

Adenoid cystic carcinoma of the salivary gland: a clinicopathological study of 49 cases and of metallothionein expression with regard to tumour behaviour

Adenoid cystic carcinoma (AdCC) of the salivary glands shows heterogeneous behaviour, with metastasis as a key indicator of poor prognosis. Metallothionein (MT) expression has been associated with poor prognosis of diverse neoplasms. We evaluated prognostic factors for AdCC and the role played by MT, focusing on metastatic behaviour.

Warthin's tumor at the Brazilian National Cancer Institute: additional evidence of homogeneous sex prevalence and association with other neoplasms.

Purpose of the Study: To report the largest Brazilian series of Warthin’s tumor (WT). Procedures: The medical files of 76 patients with WT treated in the Brazilian National Cancer Institute from 1996 to 2006 were reviewed. Results: The male:female ratio was 2:1, with a predominance of white, old, and smoking patients. However, there were more women among the nonsmokers. One fifth of the patients presented with synchronous multiple lesions. Parotid lesions were prevalent, but there were patients with lesions in cervical lymph nodes and in the inferior lip. Most cases were treated by superficial parotidectomy, without recurrences. One fourth of the patients also developed other primary neoplasms. Conclusions: The observed data do not differ from those in the international literature. Multiplicity and the development of other neoplastic diseases require close clinical management of patients with WT. Message: The previously unreported observation of female prevalence among nonsmoking people with WT should be confirmed and explored in future studies.

Metallothionein gene expression is altered in oral cancer and may predict metastasis and patient outcomes

Metallothioneins (MTs) are proteins associated with the carcinogenesis and prognosis of various tumours. Previous studies have shown their potential as biomarkers in oral squamous cell carcinoma (OSCC). Aiming to understand more clearly the function of MTs in OSCC we evaluated, for the first time, the gene expression profile of MTs in this neoplasm.

Ameloblastic carcinoma: a Brazilian collaborative study of 17 cases

Ameloblastic carcinoma (AMECA) is an odontogenic malignancy that combines the histological features of ameloblastoma and cytological atypia. Because of its rarity, it poses difficulties in diagnosis. The aim of this study was to investigate the socio‐demographic data, histopathology, immunohistochemical features, treatment and outcomes of 17 cases.

Adenoid cystic carcinoma of the maxillary sinus: a clinical-pathological report of 10 years of experience from a single institution.

Adenoid cystic carcinoma (ACC) is the most common malignant salivary gland tumour of the maxillary sinus. The present study describes 24 cases seen over a period of 10 years at the Brazilian National Cancer Institute. Socio-demographic, clinical, pathological, and follow-up data were retrieved from the medical files for the period 1997-2006. The mean age of the patients was 51.1 years. Twenty-one (87.5%) presented advanced tumours. The main signs and symptoms found were a tumour mass (87.5%), pain (50%), nasal obstruction (25%), and epistaxis (20.8%). Most cases (62.5%) were treated with surgery and radiation therapy. Follow-up data showed two patients (8.3%) with residual disease, local recurrences in four (16.7%) patients, and distant metastasis in five (20.8%). The overall 5- and 10-year survival rates were 72.61% and 62.11%, respectively. Maxillary sinus ACC has an aggressive but indolent behaviour, typically presenting at an advanced T stage that reflects a poor prognosis for patients.

Adenoid ameloblastoma: clinicopathologic description of five cases and systematic review of the current knowledge

OBJECTIVEnTo describe the clinicopathologic and immunohistochemical features of five cases of adenoid ameloblastoma.nnnSTUDY DESIGNnClinicopathologic data were gathered from medical records and compared with those compiled from a systematic review. Slides were also immunohistochemically stained for Ki-67, p16, p53, and cytokeratins (7, 8, 14, 18, and 19).nnnRESULTSnThere were 3 males (60%) and 2 (40%) females. The mean age was 44 ± 10 years. Of the five adenoid ameloblastomas, 4 (80%) occurred in the posterior maxilla. Patients typically complained of asymptomatic swelling. All patients received surgical resection as primary therapy; 1 (20%) patient also received adjuvant radiotherapy. Recurrence was diagnosed in all patients. Immunohistochemically, the tumors stained focally positive for CK7, 8, 14, and 18 and diffusely positive for CK-19, p16, and p53. The mean Ki-67-positive cells were 72.4 ± 24.9 positive cells per high-power field (range 53-111).nnnCONCLUSIONSnTo our knowledge, this is the largest series of adenoid ameloblastoma reported in the literature. Our data suggest that this entity demonstrates aggressive behavior characterized by a high likelihood of recurrence.