Profiling salivary miRNA expression levels in Fanconi anemia patients - a pilot study.

The overarching goal of this study is to predict the risk of developing oral squamous cell carcinoma (OSCC) in Fanconi anemia (FA) patients. We have compared the microRNA (miRNA, miR) expression levels in saliva samples from FA patients (n = 50) who are at a low-moderate and/or high risk of developing OSCC to saliva samples from healthy controls (n = 16). The miRNA expression levels in saliva samples were quantified using qPCR. We observed that miR-744, miR-150-5P, and miR-146B-5P had the best discriminatory capacity between FA patients and controls, with an area under the curve (AUC) of 94.0%, 92.9% and 85.3%, respectively. Our data suggest that miR-1, miR-146B-5P, miR-150-5P, miR-155-5P, and miR-744 could be used as panel to predict the risk of developing OSCC in FA patients, with a 89.3% sensitivity and a 68.2% specificity (AUC = 81.5%). Our preliminary data support the notion that the expression levels of salivary miRNAs have the potential to predict the risk of developing OSCC in FA patients and in the future may reduce deaths associated with OSCC.

Comparison of Immunohistochemistry and DNA Sequencing for BRAF V600E Mutation Detection in Mandibular Ameloblastomas.

This study aimed to investigate the presence of BRAF V600E mutation in mandibular ameloblastoma by comparing the results of molecular detection and immunohistochemical analysis. A 128 cases of mandibular ameloblastoma and 30 cases of dentigerous cyst (control group) were selected for analysis. Detection of BRAF V600E mutation was performed with immunohistochemistry (IHC) and polymerase chain reaction techniques. Clinico-pathologic data were collected in order to investigate possible associations with the mutation. Of the 128 cases submitted to IHC, 81.2% (108 cases) showed positivity for anti-BRAF V600E antibody, whereas 24 were negative (18.8%). Molecular analysis of the BRAF V600E mutation by polymerase chain reaction was possible in 116 cases due to DNA quality. Of these cases, 96 were positive (82.8%) and 20 negative (17.2%). All cases of dentigerous cyst were negative for BRAF V600E mutation in both techniques. Considering the sequencing as a gold standard method, the receiver operating characteristics curve analysis showed sensitivity of 0.99 and specificity of 1 (area under the curve=0.995, standard error=0.006; P<0.001; 95% confidence interval=0.983 to 1). We also tested the agreement between the techniques by using the Cohen's κ coefficient, with κ being 0.97 (P<0.001). IHC is a reliable test for identifying the BRAF V600E mutation in ameloblastomas, presenting advantages such as being more frequently used in surgical pathology laboratories and requiring fewer critical steps for paraffin-embedded tissue compared with molecular biology techniques.

Tobacco and alcohol-induced epigenetic changes in oral carcinoma.

PURPOSE OF REVIEW: The present review aims to describe the epigenetic alterations observed in oral cancer linked to the exposure to alcohol and/or tobacco. RECENT FINDINGS: Recent findings emphasize the importance of epigenetics in oral cancer progression and in how risk factors (as tobacco and alcohol) affect the basal epigenetic profiles. Deeper techniques and detailed approaches allowed the perception that individual CG changes and even subtle changes may represent important epigenetic alterations resulting in expression changes and other carcinogenic consequences. New classes of epigenetic alterations including noncoding RNAs have been gaining attention. SUMMARY: Many epigenetic alterations have been described in oral carcinoma progression induced by tobacco and/or alcohol, including: promoter hypermethylation in genes with tumor suppressive activity, global (genome-wide) hypomethylation, change in methylation patterns throughout the genes, alteration in noncoding RNAs, and histones modifications. These changes represent progress in the knowledge of how these risk factors act in a molecular level. There is an urgent need for large independent studies to move these potential makers further and validate them to identify risk assessment, early diagnostic markers, and therapeutic targets, as well as to be the base for prevention and intervention strategies.

Accuracy, Sensitivity and Specificity of Fine Needle Aspiration Biopsy for Salivary Gland Tumors: A Retrospective Study from 2006 to 2011

Objective: This article concerns evaluation of the sensitivity, specificity and accuracy of FNAB for pre-surgical diagnosis of benign and malignant lesions of major and minor salivary glands of patients treated in the Department of Head and Neck Surgery of Erasto Gartner Hospital. Methods: This retrospective study analyzed medical records from January 2006 to December 2011 from patients with salivary gland lesions who underwent preoperative FNAB and, after surgical excision of the lesion, histopathological examination. Results: The study had a cohort of 130 cases, but 34 cases (26.2%) were considered unsatisfactory regarding cytology analyses. Based on the data, sensitivity was 66.7% (6/9), specificity was 81.6% (71/87), accuracy was 80.2% (77/96), the positive predictive value was 66,7% (6/9) and the negative predictive value was 81.6% (71/87). Conclusion: Despite the high rate of inadequate samples obtained in the FNAB in this study the technique offers high specificity, accuracy and acceptable sensitivity.

Unusual presentation of oral amyloidosis.

Amyloidosis is a rare disease of difficult diagnosis that occurs due accumulation of amyloid substance localized or systemic. The oral cavity is an unusual site and can be related to both localized and systemic forms and for that reason a full investigation is necessary to determine the extent of the disease. This study reports a case of a 58-year-old melanoderm male patient referred to the Department of Oral and Maxillofacial Surgery with white plaques on the tongue and multiple nodules in the region of the buccal mucosa and labial commissure, with 6 months of evolution and painful symptoms. An incisional biopsy was performed on both sites and histological examination indicated the presence of eosinophilic amorphous material within the connective tissue, positive for crystal violet staining, consistent with amyloidosis. At the present time, there is no consensus on the management of local amyloidosis. Surgical treatment of localized forms is indicated in some cases to reduce the functional prejudice. Moreover, follow-up is mandatory, both to manage recurrences and to monitor the possible evolution of the disease to the systemic form.

Oral and Maxillofacial Complex Lesions in Adolescents: A Retrospective Study of 20 Years / Lesiones Orales y del Complejo Maxilofacial en Adolescentes: Un Estudio Retrospectivo de 20 Años

Studies assessing the prevalence of oral lesions show that 5.2% to 12.8% of biopsy specimens are from children and adolescents. In Brazil, there are few studies analyzing the distribution of oral lesions in that population. Therefore, the aim of this study was to evaluate the distribution of oral and maxillomandibular lesions of adolescents, admitted to the Department of Oral Diagnosis of the Federal University of Paraná (UFPR) from 1994 to 2013. A study based on the review of the charts was done and the lesions were classified in 11 categories: salivary glands disease, dental pathology, gingival and periodontal pathology, odontogenic cysts, odontogenic tumors, non odontogenic cysts, bone pathology, mucosal pathology, connective tissue pathology, malignant tumors and other pathology. Variables including age, sex, ethnicity, diagnosis and lesion location were also evaluated. Upon analysis, 376 lesions were identified, most in girls, 51.9% and 77.1 % of patients were white. The most frequent site was the lower lip followed by the gingiva. Mucocele was the most common lesion (27.6%), followed by fibroepithelial hyperplasia (8.2%) and pyogenic granuloma (5.3%). Although there is a wide range of pathologies that can occur in the oral cavity, traumatic injuries are the most common in this age group.

Los estudios que evalúan la prevalencia de lesiones orales muestran que entre el 5,2% hasta el 12,8% de las muestras de biopsia corresponden a niños y adolescentes. En Brasil, hay pocos estudios que hayan analizado la distribución de las lesiones orales enesa población. Por lo tanto, el objetivo de este estudio fue evaluar la distribución de las lesiones orales y maxilofaciales de adolescentes, ingresados en el Servicio de Diagnóstico Oral de la Universidad Federal de Paraná (UFPR) entre 1994 a 2013. Se llevó a cabo la revisión de historias clínicas y las lesiones halladas fueron clasificadas en 11 categorías: enfermedad de glándulas salivales, patología dental, patología gingival y periodontal, quistes odontogénicos, tumores odontogénicos, quistes no odontogénicos, patología ósea, patología de la mucosa, patología del tejido conectivo, tumores malignos y otras patologías. También se evaluaron otras variables como edad, género, etnia, diagnóstico y localización de la lesión. Luego del análisis, se identificaron 376 lesiones, la mayoría en niñas (51,9%), siendo el 77,1% de los pacientes de raza blanca. La localización más frecuente fue el labio inferior seguida de la encía. El mucocele fue la lesión más común (27,6%), seguido de hiperplasia fibroepitelial (8,2%) y granuloma piógeno (5,3%). Aunque existe una amplia serie de patologías que pueden ocurrir en la cavidad oral, las lesiones traumáticas son las más comunes en este grupo de edad.

Global and gene-specific DNA methylation pattern discriminates cholecystitis from gallbladder cancer patients in Chile.

AIM: The aim of the study was to evaluate the use of global and gene-specific DNA methylation changes as potential biomarkers for gallbladder cancer (GBC) in a cohort from Chile. MATERIAL & METHODS: DNA methylation was analyzed through an ELISA-based technique and quantitative methylation-specific PCR. RESULTS: Global DNA Methylation Index (p = 0.02) and promoter methylation of SSBP2 (p = 0.01) and ESR1 (p = 0.05) were significantly different in GBC when compared with cholecystitis. Receiver curve operator analysis revealed promoter methylation of APC, CDKN2A, ESR1, PGP9.5 and SSBP2, together with the Global DNA Methylation Index, had 71% sensitivity, 95% specificity, a 0.97 area under the curve and a positive predictive value of 90%. CONCLUSION: Global and gene-specific DNA methylation may be useful biomarkers for GBC clinical assessment.

Significance of p16 positive expression in oropharyngeal cancers.

BACKGROUND: The involvement of HPV in oral and oropharyngeal carcinogenesis was first proposed in 2004, based on epithelial HPV tropism and detection of HPV genotypes in oral squamous cell carcinoma samples. While 60-70% of oropharynx tumors may be HPV-positive, only 10 to 19% of tumors of the oral cavity, larynx and hypopharynx appear to have HPV infection. The aim of the study was to evaluate HPV infection associated with oropharyngeal cancer. MATERIALS AND METHODS: Seventy-eight cases were selected for p16 immunoexpression reactions, and demographic data were collected for comparisons. RESULTS: Most patients were over 60 years old, and 64.1% were smokers. Immunohistochemistry results showed that 86.3% of cases stained positive for p16 protein. CONCLUSION: The oropharyngeal cancer profile at Erasto Gaertner Hospital presented a high index of smokers over 60 years as well a high number of p16+ tumors, for what we can not determinate the main etiologic factor, but can be aware of the number of patients that presented HPV infection. Since prevention is still the best way to deal with cancer disease, it is important to analyze the interaction of these two etiologic factors and how to detect lesions at an early stage.

Retrospective study of 25 cases of keratocystic odontogenic tumor: epidemiology and treatment.

AIM: Keratocystic odontogenic tumor (KOT) is a benign odontogenic neoplasm with locally aggressive behavior and high recurrence rates. It is associated with nevoid basal cell carcinoma syndrome which usually has a more rapid growth. The aim of the study is to report the experience of our service on diagnosis and treatment of KOT. MATERIALS AND METHODS: Twenty-five cases of KOT were diagnosed between the years of 1989 and 2006. Demographic data was collected as well as diagnose and treatment. RESULTS: Fifty-six percent were female with a mean age of 33 years old. Seventy percent occurred in mandibula and all received surgical treatment, associate or not with adjuvant therapy, such as cryotherapy and Carnoy's solution. Recidive was observed in 48% of cases with a mean period of time of 18 months. CONCLUSION: Our data analysis showed the importance of previous diagnosis before enucleation procedure and long-term follow-up for recurrence early detection. Recurrence incidence is more frequent on first year after diagnosis. CLINICAL SIGNIFICANCE: KOT is a benign tumor with local aggressive behavior and therefore its treatment must consider the high index of recidive. Reports of protocol treatment should raise new discussion to decrease recurrence rates.

Altered ß-catenin expression related to cancer progression on actinic cheilitis and squamous cell carcinoma of the lip.

ß-Catenin is a bifunctional protein related to cell adhesion and gene transcription when activated by Wnt pathway. Altered expression of ß-catenin was related to loss of differentiation, more aggressive phenotype, increase of tumor invasion, and poor prognosis in a number of different cancers. Actinic cheilitis is caused by excessive exposure to ultraviolet radiation and has a high potential to suffer malignant transformation into squamous cell carcinoma (SCC) of the lip, the most frequent oral malignancy. Studies of oral cancer have shown the correlation of ß-catenin expression and oral SCC prognosis, and loss of membrane expression may be considered as a potential marker for early tumor recurrence. Thirty-five cases of actinic cheilitis and 12 cases of SCC of the lip were select and submitted to immunohistochemical staining using ß-catenin antibody. ß-Catenin was positive on the membrane for all cases. Eighty-five percent of actinic cheilitis cases showed cytoplasmatic staining, and 22% nuclear staining. Eighty-three percent of SCC was positive for ß-catenin, and none of them had nuclear staining. Cytoplasmatic and nuclear staining of ß-catenin on studied cases point to pathway alterations. Results demonstrated that ß-catenin expression is altered on epithelial dysplasia, and it is related to degree of alterations.