High frequency of microsatellite instability in young patients with head-and-neck squamous-cell carcinoma: Lack of involvement of the mismatch repairgenes hMLH1 and hMSH2
Ym. Wang et al., High frequency of microsatellite instability in young patients with head-and-neck squamous-cell carcinoma: Lack of involvement of the mismatch repairgenes hMLH1 and hMSH2, INT J CANC, 93(3), 2001, pp. 353-360
The most prevalent risk factors in the development of head-and-neck squamou
s-cell carcinoma (HNSCC) are excessive tobacco and alcohol consumption, In
young patients with HNSCC, these risk factors are often absent. Our purpose
was to investigate the risk factors, microsatellite instability (MSI) chan
ges and status of the mismatch repair genes hMLH1 and hMSH2 in a cohort of
young patients with HNSCC. Fifty-seven HNSCC tumors were examined for the p
resence of MSI at 16 microsatellite sites using PCR. In the young patient g
roup (24 cases, less than or equal to 44 years old), 100% of tumors had MSI
at 1 site at least and 88% had MSI at 2 or more loci, In older patients (3
3 cases, greater than or equal to 45 years), MSI at I or more sites was fou
nd in 61 % of tumors (young vs, old, p = 0.0003) and instability at 2 or mo
re sites was found in 36% of tumors (young vs. old, p = 0.0001), The involv
ement of the mismatch repair genes was investigated by examining promoter m
ethylation, exon mutation and gene expression of hMLH1 and hMSH2, All resul
ts were negative, indicating that inactivation of these 2 genes does not pl
ay a role in the development of MSI in tumors from this patient group. Furt
hermore, the young patient group had a significantly lower incidence of sme
lting (46% young. 88% old; P = 0.001) and alcohol consumption (33% young, 6
7% old; p = 0.0169), emphasizing the probable importance of other environme
ntal and/or genetic factors in the development of their disease. (C) 2001 W
iley-Liss, Inc.