Monitoring of circulating tumour-associated DNA as a prognostic tool for oral squamous cell carcinoma

Abstract

Frequent allelic imbalances (AIs) including loss of heterozygosity and microsatellite instability on a specific chromosomal region have been identified in a variety of human malignancies. The objective of our study was to assess the possibility of prognostication and monitoring of oral squamous cell carcinoma (SCC) by microsatellite blood assay. DNA from normal and tumorous tissues and serum DNA obtained at three time points (preoperatively, postoperatively, and 4 weeks postoperatively) from 64 patients with oral SCC was examined at nine microsatellite loci. In all, 38 (59%) DNA samples from tumorous tissues and 52% from serum showed AIs in at least one locus. Patterns of AIs in the serum DNA were matched to those detected in tumour DNA. Of them, AIs were frequently detected preoperatively (44%, 28 of 64), and postoperatively (20%, 13 of 64). Moreover, among 12 cases with AIs during the postoperative period, six had no evidence of an AI 4 weeks postoperatively, and they had no recurrence and were disease free. In contrast, six patients with AI-positive DNA 4 weeks postoperatively have died with distant metastasis within 44 weeks. Thus, our results suggest that the assessment of microsatellite status in the serum DNA could be a useful predictive tool to monitor disease prognosis.

Figure 1

Representative results of the microsatellite analysis at the IFNA locus of a lymphocyte (lane 1), preoperative sera (lane 2), postoperative sera (lane 3), sera 4 weeks postoperatively (lane 4), and tumour (lane 5) from a patient with oral SCC (case P24). While DNA from lymphocyte reveals two major silver-stained bands, LOH of top alleles are detected in DNA from sera at all time points and from tumour tissue.