Microsatellite instability and abnormal mismatch repair in laryngeal squamous cell carcinoma / 中国耳鼻咽喉头颈外科

ABSTRACT

OBJECTIVE The aim of our study was to evaluate the significance of the frequency of microsatellite instability (MSI) and its relationship to mismatch repair gene (MMR) in laryngeal squamous cell carcinoma.METHODS We investigated the expression frequency and clinical significance of MSI and MMR in 50 laryngeal squamous cell carcinoma (LSCC) patients from Beijing Tongren Hospital. The status of MSI was evaluated using microdissection - polymerase chain reaction (PCR) - single strand length polymorphism (SSLP) - silver staining.Five markers on chromosomes 1p, 3p, 5q, 9p, 17p, which were adjacent to BCAR3 (breast cancer anti-estrogen resistance 3), FHIT, APC, CDKN2A (p16), TP53 respectively, were used. Two of the six components of MMR -hMLH1 and hMSH2- were investigated by an immunohistochemical approach because of the high frequency of their downregulation in head and neck tumors. RESULTS The informative case number of the five markers (D17S796, D3S3544, D5S656, D1S375, D9S162) were 44, 42, 45, 44 and 40 respectively. The incidence of MSI was lower than the frequency of loss of heterozygosity (LOH). The incidence of MSI on D17S796 (TP53)was 20.5% (9/44),on D3S3544 (FHIT) was 14.3 % (6/42), on D5S656 (APC) was 31.1% (14/45), on D1S375 (BCAR3) was 20.5 % (9/44), and on D9S162 (CDKN2A) was 15.0 % (6/40). Though there was no relationship between MSI status and age, gender, smoke history, tumor location, tumor differentiation and T stage (P＞0.05),there was a strong correlation between MSI and relapse condition (P＜0.01). Also, MSI status correlated with MMR expression to some degree (P＜0.01), but it was common for negative and positive staining of MMR to coexist on the same slide. CONCLUSION Microsatellite instability and abnormal mismatch repair may contribute to the carcinogenesis of a subset of laryngeal squamous cell carcinoma. Microsatellite instability may be a characteristic signal of tumor recurrence.