Joanne L. Prasad

Insights from Studies with Oral Cleft Genes Suggest Associations between WNT-pathway Genes and Risk of Oral Cancer

Oral squamous cell carcinoma (OSCC) accounts for more than 90% of the malignant neoplasms that arise in the mucosa of the upper aerodigestive tract. Recent studies of cleft lip/palate have shown the association of genes involved in cancer. WNT pathway genes have been associated with several types of cancer and recently with cleft lip/palate. To investigate if genes associated with cleft lip/palate were also associated with oral cancer, we genotyped 188 individuals with OSCC and 225 control individuals for markers in AXIN2, AXIN1, GSK3β, WNT3A, WNT5A, WNT8A, WNT11, WNT3, and WNT9B. Statistical analysis was performed with PLINK 1.06 software to test for differences in allele frequencies of each polymorphism between cases and controls. We found association of SNPs in GSK3B (p = 0.0008) and WNT11 (p = 0.03) with OSCC. We also found overtransmission of GSK3B haplotypes in OSCC cases. Expression analyses showed up-regulation of WNT3A, GSK3B, and AXIN1 and down-regulation of WNT11 in OSCC in comparison with control tissues (P < 0.001). Additional studies should focus on the identification of potentially functional variants in these genes as contributors to human clefting and oral cancer.

Interaction between IRF6 and TGFA Genes Contribute to the Risk of Nonsyndromic Cleft Lip/Palate

Previous evidence from tooth agenesis studies suggested IRF6 and TGFA interact. Since tooth agenesis is commonly found in individuals with cleft lip/palate (CL/P), we used four large cohorts to evaluate if IRF6 and TGFA interaction contributes to CL/P. Markers within and flanking IRF6 and TGFA genes were tested using Taqman or SYBR green chemistries for case-control analyses in 1,000 Brazilian individuals. We looked for evidence of gene-gene interaction between IRF6 and TGFA by testing if markers associated with CL/P were overtransmitted together in the case-control Brazilian dataset and in the additional family datasets. Genotypes for an additional 142 case-parent trios from South America drawn from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), 154 cases from Latvia, and 8,717 individuals from several cohorts were available for replication of tests for interaction. Tgfa and Irf6 expression at critical stages during palatogenesis was analyzed in wild type and Irf6 knockout mice. Markers in and near IRF6 and TGFA were associated with CL/P in the Brazilian cohort (p<10−6). IRF6 was also associated with cleft palate (CP) with impaction of permanent teeth (p<10−6). Statistical evidence of interaction between IRF6 and TGFA was found in all data sets (p = 0.013 for Brazilians; p = 0.046 for ECLAMC; p = 10−6 for Latvians, and p = 0.003 for the 8,717 individuals). Tgfa was not expressed in the palatal tissues of Irf6 knockout mice. IRF6 and TGFA contribute to subsets of CL/P with specific dental anomalies. Moreover, this potential IRF6-TGFA interaction may account for as much as 1% to 10% of CL/P cases. The Irf6-knockout model further supports the evidence of IRF6-TGFA interaction found in humans.

Psammomatoid and trabecular juvenile ossifying fibroma: two distinct radiologic entities

OBJECTIVE Evaluate and compare the radiologic features of psammomatoid versus trabecular variants of juvenile ossifying fibromas. STUDY DESIGN Twelve of fifteen cases of juvenile ossifying fibroma of the craniofacial bones, retrieved from our pathology archives for the period between 2002 and 2013, had available preoperative computed tomography (CT) scans. The radiologic features of each case were analyzed and compared by two neuroradiologists and one oral and maxillofacial radiologist, each blinded to the histopathologic diagnosis. RESULTS Juvenile psammomatoid ossifying fibroma (JPOF) exhibited a ground-glass pattern, as an outer mantle with central radiolucency, a single mural nodule, or a solid homogeneous mass. The trabecular variant presented as a radiolucent lesion with irregular, scattered calcifications. Both variants displayed a well-defined border. CONCLUSION This study demonstrates that psammomatoid and trabecular juvenile ossifying fibromas exhibit unique radiologic features that allow for distinction between the two variants on CT studies.

Molecular Diagnostics for Head and Neck Pathology

Molecular diagnostic techniques are quickly finding a role in the detection and diagnosis of tumors, and in predicting their behavior. They may also prove useful in developing new therapeutic approaches to head and neck cancer. The surgeon working in the craniomaxillofacial region should have an understanding of these technologies, their availability in various settings, and how they affect various aspects of treatment, particularly in the detection and treatment of malignancies. This article offers an overview of recent advances in molecular diagnostic techniques, with their implications for diagnosis and management of head and neck tumors.

Oral hairy leukoplakia in patients without HIV: presentation of 2 new cases

OBJECTIVE We report 2 cases of oral hairy leukoplakia (OHL) in patients without HIV and present a comprehensive review of OHL in HIV-negative individuals. STUDY DESIGN Two cases of non-HIV-associated OHL are described. A PubMed search identified previously reported cases. The attributes of those cases were ascertained. RESULTS OHL was confirmed in both of our cases. Both patients used inhaled steroids for pulmonary disorders, and were found to have depressed levels of immunoglobulin M. Additionally, 76 cases were identified in the literature. The condition occurred in association with various medical conditions, with the majority of patients on immunosuppressant medications (67 of 76). Systemic drugs were implicated most frequently. The condition has also been reported in healthy individuals (6 of 76). CONCLUSIONS Although thought of as an HIV/AIDS-associated condition, OHL can develop in patients without HIV, including healthy individuals. There is a strong correlation between the use of immunosuppressants and development of OHL in these patients.

Is Computed Tomography an Adequate Imaging Modality for the Evaluation of Juvenile Ossifying Fibroma? A Comparison of 2 Imaging Modalities (Computed Tomography and Magnetic Resonance Imaging)

PURPOSE Given the problems of overuse of medical technology and the current burden of health care cost in the United States, it is important to establish clear imaging guidelines to diagnose conditions such as juvenile ossifying fibroma (JOF). This study compared the efficacy of computed tomography (CT) and magnetic resonance imaging (MRI) in the evaluation of JOF and thus could aid establishing such guidelines. MATERIALS AND METHODS Radiologic criteria were established by 2 radiologists to compare the efficacy of CT and MRI in the evaluation of JOF. The following parameters were compared: presence of a well-defined corticated border, presence of a well-delineated internal calcified component, fluid-to-fluid levels, and anatomic extent of the lesion. Six patients diagnosed with JOF of the craniofacial bones from 2002 to 2013 had preoperative CT and MRI studies available for review. RESULTS After review of CT and MRI images, fluid-to-fluid levels and anatomic extent of the lesions were comparable on CT and MRI. However, the corticated borders and the internal calcified component were better defined on CT images, which also enabled for distinction between the 2 subtypes of JOF. No MRI characteristics were identified that allowed for this distinction. CONCLUSION Based on these findings, CT is an adequate and preferable imaging modality in the evaluation of JOF.

Molecular and Genetic Aspects of Odontogenic Lesions

In this article we outline the molecular findings of select odontogenic tumors. In each section, we briefly review selected the clinicoradiographic, histologic, immunologic features, focusing on the molecular findings and their applications in practice. The understanding of molecular pathobiology at various other organ sites has developed quite rapidly in recent years, however much remains unknown about the genetic profile of odontogenic tumors. Improved understanding of mutations in odontogenic tumors may clarify classification schema and elucidate targets for novel therapies. Molecular testing will no doubt improve our understanding of odontogenic tumor pathogenesis and will likely be, someday, an important component of routine clinical practice and its role will only increase in the coming years.