The human ELAV(embryonic lethal abnormal vision)-like protein HuR stabilizes a certain group of cellul ar mHNAs that contain AU- rich elements in their 3’ - untranslated region , To test the significance of HuR in carcinogenesis of head and neck squamous cell carcinomas(HNSCCs), we have investigated HuH expression from 32 benign epithelial lesions , 14 prema lignant epitheli al lesions and 80 HNSCCs, There were two different staining patterns of HuR in HNSCCs : nuclear expression was seen in 78 7% (63 of 80) 01' cases; and an additional cyto plasmic expression was seen in 28, 7%(23 of 80) 01 cases, Nuclear expression of HuR was s ignificantly increased in premalignant lesions and HNSCCs, whereas increased cytoplasπli c expression of HuR was only observed in HNSCCs Cytoplasmic HuR expression was significantly increased in pa tients of HNSCC younger than 60 yea rs , Al though there was no significant correlation between a natomic s ites of HNSCCs and HuR express ion , cyto plasmic HuR expression was highly increased in HNSCCs of larynx, There was no significant co rrela tion between HuR expression and other clinicopathological parameters such as histological type‘ tumor s ize‘ 0 1' n odal s tatus , ln conclusion, this study s uggests that overexpression of HuR in HNSCCs may be part of a regula tory pathway tha t co ntro ls the mHNA stability 0 1' several important targets in carcinogenesis of HNSCCs

Expression of invasion/metastasis suppressor, E-cadherin, is reduced in many types of human carcinomas. Although somatic and germline mutations in the CDH1, which encodes the human E-cadherin, have frequently been reported in cases with diffuse gastric and lobular breast cancers, irreversible genetic inactivations are rare in other human carcinomas. Recently, it has been well documented that some genes in human cancers may be inactivated by altered CpG methylation. Herein, we determined the expression and methylation status of E-cadherin in oral squamous cell carcinoma(SCC) by immunohistochemistry and methylation-specific PCR. The expression of E-cadherin was significantly higher in the well-differentiated oral SCCs than the moderately or poorly differentiated ones. None of eight tested benign epithelial hyperplasias showed aberrant methylation, whereas five of 12 oral squamous cell carcinomas showed aberrant methylation. When we compared E-cadherin expression with methylation status, oral SCCs with normal methylation showed a higher expression of E-cadherin than those with methylation. These findings suggest that aberrant CpG methylation of CDH1 promoter region is closely associated with transcriptional inactivation and might be involved in tumor progression of the oral mucosa.

To cletermine the role of mismatch repair in the clevelopment of oral squamolls cell carcinomas (OSCCs) , the prevalence of microsatellite instability (MSI), expression of I뼈LH1 ancll띠SH2 ， ancl hypennethylation of I뻐LH1 ancl hMSH2 were explorecl. Bya panel of five markers (BAT25, BAT26 , 02S123, 05S346, ancl 017~‘250 ， the so-callecl Bethescla markers) for screening of MSI, MSI was observecl in 5 of the 15 sqllamolls cell carcinomas (33.3%). As MSI is callsecl by the clysfllnction of MMR genes, this stucly examinecl the methylation status of CpG sites in the hMLH 1 ancl hMSH2 promoters ancl the expression hMLH1 ancl hMSH2. Becallse of inappr이)riate efficiency of fonnalin-frxecl ancl paraffin-embeclclecl samples for methylation-specific PCR (MS-PCR) of hMLH1 ancl hMSH2, the role of promoter hypelmethylation 띠 the clevelopment of MSI ancl expression of hMLH1 ancl hMSH2. meùlylation was failecl to clefìne. However, loss of nllclear staining of 1ψIILH 1 ancl hMSH2 were seen in nine (69.2%) ancl four (30.7%) of 13 OSCCs, while four ancl fìve all corresponcling normal epiùlelial tisslles showecl positive nllclear stι ining ofl마ILH1 and hMSH2. These data suggest that MSI anclloss of expression of hMLH1 ancl hMSH2 play a role in the carcinc핑enesis of oral sqllamolls cell carcinomas thollgh the role of promoter hypermethylation of hMLH1 ancl hMSH2 in MSI and their expresslon IS lIncertam