Embryonal Rhabdomyosarcoma of the Oral Cavity
HEAD & NECK PATHOLOGY
Authors: McInturff, Mark; Adamson, Anne; Donaldson, Chadwick; Nelson, Brenda L.
Abstract
A 19 year old female presents to the emergency room with right facial enlargement. Clinical examination revealed a soft tissue mass of the right buccalmucosa. Treated initially as infection, the patient later turned to clinic with now rapidly enlarging and intermittently painful mass. Computed tomography with contrast showed a low attenuated buccal mass with mild enhancement lateral to the right caudal maxilla and superior mandible. Biopsy was performed and microscopic examination showed cells with moderate pleomorphism with numerous atypical mitotic figures and occasional elongated "strap" cells with eccentric nuclei. Fluorescence in situ hybridization analysis revealed no rearrangement of the FKHR gene. The diagnosis of embryonal rhabdomyosarcoma was rendered. The patient was referred to the local children's hospital for definitive treatment.
Establishment of epigenetic markers to predict irradiation efficacy against oropharyngeal cancer
CANCER SCIENCE
Authors: Kurokawa, Tomoya; Nakagawa, Takuya; Matsusaka, Keisuke; Fukuyo, Masaki; Mima, Masato; Misawa, Kiyoshi; Rahmutulla, Bahityar; Ikeda, Jun-ichiro; Hanazawa, Toyoyuki; Okamoto, Yoshitaka; Kaneda, Atsushi
Abstract
Irradiation, or chemoradiotherapy, is a curative treatment for oropharyngeal squamous cell carcinoma (OPSCC). Its invasiveness, however, can often negate its efficacy. Therefore, developing methods to predict which patients would benefit from irradiation is urgent. Promoter DNA hypermethylation was recently reported to correlate with favorable OPSCC prognosis. It is still unclear, however, whether there is an association between promoter DNA methylation and response to irradiation. In this study, we analyzed DNA methylation in the specimens from 40 OPSCC patients who had undergone irradiation, using the Infinium assay. Our results showed significant correlation between high levels of promoter DNA methylation and better response to treatment (P < 0.01). We used the 10 most differentially-methylated genes between responders and non-responders to develop a panel of predictive markers for efficacy. Our panel had high sensitivity, specificity and accuracy (92%, 93% and 93%, respectively). We conducted pyrosequencing to quantitatively validate the methylation levels of 8 of the 10 marker genes (ROBO1, ULK4P3, MYOD1, LBX1, CACNA1A, IRX4, DPYSL3 and ELAVL2) obtained by Infinium. The validation by pyrosequencing showed that these 8 genes had a high prediction performance for the training set of 40 specimens and for a validation set of 35 OPSCC specimens, showing 96% sensitivity, 89% specificity and 94% accuracy. Methylation of these markers correlated significantly with better progression-free and overall survival rates, regardless of human papillomavirus status. These results indicate that increased DNA methylation is associated with better responses to irradiation therapy and that DNA methylation can help establish efficacy prediction markers in OPSCC.