RAB25 expression is epigenetically downregulated in oral and oropharyngeal squamous cell carcinoma with lymph node metastasis

Oral and oropharyngeal squamous cell carcinoma (OOSCC) have a low survival rate, mainly due to metastasis to the regional lymph nodes. For optimal treatment of these metastases, a neck dissection is required; however, inaccurate detection methods results in under- and over-treatment. New DNA prognostic methylation biomarkers might improve lymph node metastases detection. To identify epigenetically regulated genes associated with lymph node metastases, genome-wide methylation analysis was performed on 6 OOSCC with (pN+) and 6 OOSCC without (pN0) lymph node metastases and combined with a gene expression signature predictive for pN+ status in OOSCC. Selected genes were validated using an independent OOSCC cohort by immunohistochemistry and pyrosequencing, and on data retrieved from The Cancer Genome Atlas. A two-step statistical selection of differentially methylated sequences revealed 14 genes with increased methylation status and mRNA downregulation in pN+ OOSCC. RAB25, a known tumor suppressor gene, was the highest-ranking gene in the discovery set. In the validation sets, both RAB25 mRNA (P = 0.015) and protein levels (P = 0.012) were lower in pN+ OOSCC. RAB25 mRNA levels were negatively correlated with RAB25 methylation levels (P < 0.001) but RAB25 protein expression was not. Our data revealed that promoter methylation is a mechanism resulting in downregulation of RAB25 expression in pN+ OOSCC and decreased expression is associated with lymph node metastasis. Detection of RAB25 methylation might contribute to lymph node metastasis diagnosis and serve as a potential new therapeutic target in OOSCC

CARBON-DIOXIDE LASER-SURGERY OF ORAL LEUKOPLAKIA

Oral leukoplakia is a precancerous lesion of the oral mucosa. The risk of malignant transformation depends on the clinical and histologic classification and the location of the lesion. For a nonhomogeneous leukoplakia, this risk is 23.4% to 38.0%. In the presence of epithelial dysplasia, the possibility of malignant transformation is 36.3% to 43.0%. Leukoplakia is limited to the epithelium, so a selective removal of this part of the mucosa seems to be the best preventive treatment. Carbon dioxide laser surgery accomplishes a superficial removal by evaporation. A total of 70 patients with 103 oral leukoplakias were treated with carbon dioxide laser evaporation. This resulted in an excellent wound healing with virtually no scarring. The patients were followed up during a period of up to 12 years (mean 5.3 years), showing a cure rate of 90%

Mandibulotomy and implant insertion

Background. A mandibulotomy can be necessary to approach a tumor in the oral cavity or oropharynx. The aim of this study was to develop and prospectively evaluate a technique enabling simultaneous performance of a mandibulotomy and insertion of endosseous implants in the same area. Methods. In five edentulous patients such a procedure was performed. The pilot drilling of the implants was done before performing the mandibulotomy. After tumor resection, reconstruction, and restoration of the continuity of the mandible, the final drilling and insertion of the implants were completed. In total, 20 implants were inserted. All patients received radiation therapy within 6 weeks after surgery. Implant-supported overdentures were fabricated 6 months after irradiation. At regular time intervals, a standardized clinical and radiographic evaluation was performed. Results. No complications with respect to the combination of implant insertion and mandibulotomy were observed either during or after surgery. In addition, no adverse mucosal reactions were observed during the course of radiotherapy, no cases of osteoradionecrosis developed, and no implants were lost. Clinical and radiographic evaluation revealed healthy peri-implant parameters. Conclusion. From this study it is concluded that, when following the technique described, a mandibulotomy can be combined safely with the insertion of implants in the ventral part of the edentulous mandible. (C) 2003 Wiley Periodicals, Inc