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

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.

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 ³² 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.

Using 65% cutoff LOH-FCE, the agreement of LOH-³² 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.

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.