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

Publication date: Available online 18 December 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Kelly Y.P. Liu, X.J. David Lu, Yi-Shing L. Cheng, Hagen Klieb, Samson Ng, Kelly McNeil, Aly Karsan, Catherine F. Poh
Objectives.To develop an actionable test using fluorescent-labeled primers with capillary gel 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 cut-offs of LOH, the FCE results of 52 surgical margin samples were used to compare to the existing LOH results from the previously validated ³²P-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% cut-off LOH-FCE, the agreement of LOH-³²P-GE showed an average of 82.3% (76.8-87.8). Comparing to non-progressors (n=61), anatomical site, and MR patterns (LOH at 9p21, 3p14, or 17p13) were independent risk factors. High-risk profile of tongue and MR3 (LOH at 9p21 and/or 3p14, and 17p13) was significantly associated with progression (HR, 6.7; 95% CI, 2.6-17.6) with specificity of 98.4% at identifying progressors.Conclusions.We have developed an objective, fast, environmental-safe, and cost-effective 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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