Microsatellite alterations in esophageal dysplasia and squamous cell carcinoma from laser capture microdissected endoscopic biopsies

Abstract

Esophageal squamous cell carcinoma (ESCC), with a 5 year survival below 15%, is one of the most common fatal cancers worldwide. Significant reduction in mortality may be achieved by detecting and treating asymptomatic precursor lesions and curable early cancers. To explore this possibility and look for potential early detection markers, we examined alterations in 16 microsatellite markers in laser capture microdissected (LCM) endoscopic biopsies from the esophagus, including 15 dysplasias and 22 ESCCs, in patients from Shanxi Province, a region in north-central China. We found a significant increase in the total frequency of allelic loss with increasing disease severity. Allelic loss was seen in 2% of the markers in patients with low grade dysplasia (LGD), 15% of the markers in patients with high grade dysplasia (HGD), and 35% of the markers in patients with ESCC. Ten different markers (D3S4513, D5S2501, D8S1106, D9S118, D9S910, D13S1493, D13S894, D13S796, D15S655, and D17S1303) showed allelic loss in one or more of the premalignant lesions tested. The frequency of microsatellite instability (MSI) also increased with histological severity, from 22% in LGD to 33% in HGD and 59% in ESCC. These results indicate that the development of ESCC is associated with genetic instability, that this instability can be detected in endoscopic biopsies of recognized precursor lesions in patients without invasive cancer, and that these markers may be useful as predictive markers in the early detection of ESCC. Finally, we also report methodologic/technical modifications that enhance the use of LCM for screening endoscopic biopsies.