Microsatellite instability as an indicator of malignant progression in laryngeal premalignancy

Abstract

Microsatellite instability (MSI) is considered a novel marker of genetic instability, and preliminary studies have shown that it may provide useful information in assessing the risk of malignant progression in preinvasive lesions. We analyzed MSI in serial biopsy specimens from 10 patients with preinvasive laryngeal lesions and corresponding metachronous laryngeal cancers compared with biopsy specimens of similar lesions without malignant transformation from 20 subjects in a match-paired analysis. MSI was determined by assessing the status of 14 microsatellite markers (chromosome loci: 2p16, 3q21-24, 4q12, 9p21, 13q14, 16q22.1, 17p12 and 21q21) in DNA biopsy specimens. MSI(+) (aberration at two or more loci) was detected in seven of 10 patients with premalignant lesions progressed to carcinoma, whereas only four of the 20 biopsy specimens from control subjects showed an unstable phenotype (p < .01). Interestingly, preinvasive laryngeal lesions with MSI at hMSH2/hMSH6 loci frequently had instability at one or more additional loci and were considered as MSI(+) (overall in eight of 12 cases: six premalignant lesions progressed to cancer and one without progression of the original laryngeal lesion, p < .01). The immunohistochemical analysis of the hMSH2 protein expression in our series, however, did not suggest its involvement in laryngeal carcinogenesis. Our study indicates that MSI is more common in preneoplastic laryngeal lesions progressing to cancer, thus suggesting that microsatellite status assessment may be useful in determining the risk of malignant progression in patients with preinvasive laryngeal lesions for whom chemopreventive and multiple endoscopic protocols can be attempted.