Using loss of heterozygosity of microsatellites to distinguish high-grade dysplastic nodule from early minute hepatocellular carcinoma.

Background: It is practical significant to seek new applicable adjuvant diagnostic biomarkers to differentiate high-grade dysplastic nodule (HGDN) from well-differentiated minute hepatocellular carcinoma (w-MHCC) due to their closely overlapping morphology.

Methods: In the present study, by using microdissection-based paraffin-embedded tissues, loss of heterozygosity (LOH) patterns of a panel of 22 microsatellite (MS) markers was examined in 8 HGDN, 14 w-MHCC (≤1 cm) and 35 larger HCC (LHCC, >1 cm).

Results: The results revealed a stepwise increasing fractional allelic loss from HGDN, w-MHCC and LHCC (0.166±0.141, 0.377±0.198, 0.471±0.264, respectively, P=0.005). Loci-specific analyses showed that LOH on D4S415 (66.7% vs 0.0%, P=0.04), D1S507 (50.0% vs 0.0%, P=0.098), and D9S1752 (50.0% vs 0.0%, P=0.33) occurred more frequently than 50% in w-MHCC, but not in HGDN. On the other hand, LOH on D17S960, D17S1796 and D9S1749 occurred in HGDN, but not in w-MHCC. When compared with w-MHCC, LHCC had a higher LOH frequency on D17S720 (73.9% vs 36.4%, P=0.04), D17S960 (68.8% vs 0.0%, P=0.03) and D17S1796 (81.8% vs 0.0%, P=0.01).

Conclusions: The present study suggests MS-LOH is a simple and specific assay for routinely diagnostic pathology. We recommend that D4S415, D1S507, D9S1752, D17S960, D17S1796 and D9S1749 can be used as the first-line markers for differential diagnosis between HGDN and w-MHCC, and D9S1748, D17S921 and D17S520 with a LOH frequency of 40%-50% in w-MHCC, but netative in HGDN, can be regarded as the second-line candidate markers.