An actionable test using loss of heterozygosity in identifying high-risk oral premalignant lesions.

Oral Surg Oral Med Oral Pathol Oral Radiol

Department of Oral Medical Biological Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada; Department of Integrative Oncology, BC Cancer Agency, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Published: December 2017

Objectives: To develop an actionable test using fluorescence capillary electrophoresis (FCE) to assess loss of heterozygosity (LOH) of histologically similar low-grade lesions (LGLs) to identify high-risk lesions for oral cancer progression.

Study Design: To determine the cutoffs of LOH, the FCE results of 52 surgical margin samples were used to compare with the existing LOH results from the previously validated P-GE approach. Using the developed FCE workflow, an independent set of 102 LGLs with known progression status was used to determine the LOH molecular risk (MR) patterns and associated risk of progression.

Results: Using 65% cutoff LOH-FCE, the agreement of LOH- P-GE had an average of 82.3% (76.8-87.8). Compared with nonprogressors (n = 61), anatomic site and MR patterns (LOH at 9 p21, 3 p14, or 17 p13) were independent risk factors. High-risk profile of tongue and MR3 (LOH at 9 p21 and/or 3 p14 and 17 p13) was significantly associated with progression (hazard ratio [HR] 6.7; 95% confidence interval [CI] 2.6-17.6) with specificity of 98.4% at identifying progressors.

Conclusions: We have developed an objective test using LOH to stratify the risk of LGLs. With further validation, it can be used in the clinical settings to provide clinicians additional information guiding the management of these lesions.

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http://dx.doi.org/10.1016/j.oooo.2017.10.019DOI Listing

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