Prevalence of microsatellite instability, inactivation of mismatch repair genes, p53 mutation, and human papillomavirus infection in Korean oral cancer patients.
To determine the etiologic factors of human oral cancer, we examined the prevalence of microsatellite instability (MSI), the inactivation of mismatch repair (MMR) genes, p53 mutation, and human papillomavirus (HPV) infection (HPV-16, -18, and -33) in 86 Korean oral cancer specimens, including 76 squamous cell carcinomas and 10 salivary gland tumors. MSI was observed in 3 of the 76 squamous cell carcinomas (4%) and 2 of 10 salivary gland tumors (20%). As MSI is a hallmark of the inactivation of the MMR genes, the genetic status of hMSH2 and hMLH1, and hypermethylation of the hMLH1 promoter region were investigated in oral cancers displaying MSI. Inactivation of the hMLH1 gene by either mutation or hypermethylation was observed 4 of the 5 MSI oral cancers. Mutation of the p53 gene was found in 11 of 76 squamous cell carcinomas (14.5%) but not in the salivary gland tumors. PCR assay revealed the presence of HPV DNA in 11 of the 76 squamous cell carcinomas (14.5%) and 4 of the 10 salivary gland tumors (40%). Type 18 HPV DNA was predominant in 11 of the HPV-infected squamous cell carcinomas (72.7%) and 4 of the HPV-infected salivary gland tumors (50%). Two squamous cell carcinoma tissues were found both to be HPV-infected and to harbor the p53 mutation. Our results suggest: i) that MSI plays a role in the pathogenesis of Korean oral cancers, squamous cell carcinomas (4%) and salivary gland tumors (20%); ii) that genetic alteration or hypermethylation of the hMLH1 gene may be the principal inactivating mechanism in Korean oral cancer with MSI; and iii) that inactivation of the p53 gene by either mutation or HPV infection is frequent in Korean squamous cell carcinomas (26%) and salivary gland tumors (40%).
BK21 HLS, College of Dentistry Seoul National University, Seoul, Korea.
Ki-Hyuk
KH
Shin
Kyung-Hee
KH
Park
Hyun Jon
HJ
Hong
Jin-Man
JM
Kim
Ju-Eun
JE
Oh
Pill-Hoon
PH
Choung
Byung-Moo
BM
Min
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D020137:Base Pair Mismatch; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics / Q000473:pathology; D002352:Carrier Proteins; D002648:Child; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012468:Salivary Gland Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014412:Tumor Virus Infections / Q000150:complications*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein