| IntroductionOvarian cancer are the third commonest in gynecological malignancies.Ovarian cancer continues to be the foremost cause of mortality.Because of the inaccessible location of the ovary and lack of effective early diagnosis,the majority of patients with ovarian cancer present advanced disease.Therefore,study on carcinogenesis of ovarian cancer has a significance in the development early diagnosis and novel therapy.Ninety percent of ovarian cancers are epithelial cancers.The most popular hypothesis about the development of ovarian epithelial tumors is that they originate from small epithelial inclusion cysts.The surface epithelial is derived from the coelomic epithelium,vvhich gives rise to the mUllerian ducts,it is accepted that the surface epithelium is capable of differentiating into serous,mucinous,endometrioid or transitional epithelium. It is unclear whether ovarian carcinomas develop from malignant transformation of benign precursors or they arise de novo.Mismatch repair genes are housekeeping genes. In Hereditary Nonpolyposis Colonrectal Cancer (HNPCC),mismatch repair(MMR) gene deficiency speeds up multistep process. This defect is attributed to germ line mutations in the DNA mismatch repair genes.mainly hMLHl and /iMS7/2.However,MMR mutations were found in less than 10% of sporadic MSI(microsatellite instability) tumors. The reason for this lack of MMR mutations is the transcriptional inactivation of hMLHl by promoter hypermethylation.Methylation is the main epigenetic modification in mammals and abnormal methylation of theCpG islands located in the promoter region or the genes leads to transcriptional silencing.A tight correlation between the presence of hMLHl promoter hypermethylation and MSI in colorectal,endometrium and gastric tumors has been demonstrated.The above three tumour types are common in HNPCC patients. Hypermethylation of hMLHl promoter,documented by methylation-specific polymerase chain reaction,restriction cut analysis and sequencing,occurs in the context of a hMLHl gene without mutation and correlates with the lack of hMLHl expression at RNA and protein level .No evidence of aberrant methylation of other MMR gene such asHMSH2,hMSH3 and hMSH6 has been found so far.In cancer cell lines,demethylating agents are not only able to reactivate the hMLHl gene,but are to restore the mismatch repair activity.As expected,/zML//7 promoter hypermethylation is an early aleration,appearing in the premilignant stages of processes such as atypical endometrial hyperplasia,ulcerative colitis lesions and gastric adenoma.Tumorigenesis is a multistep process involving alterations of differtent oncogenes and tumor suppressor genes.Models for the sequential steps of the genetic changes involved in tumor development have been proposed for certain cancers,such as colon cancer. In the case of ovarian cancer,relatively little is known about the genetic events initiation or subsequent progression and metastases of the tumor.Ovarian mucinous tumor can be classified into two types:a pure endocervical type and a mixed intestinal endocervical type.There is evidence indicating that malignant epithelial may sometimes result from the progressive transformation of bengin and/or borderline tumors. In fact benign epithelium is histologically found in 90% of mucinous cystadenocarcinoma. Serous subtype is more common than mucinous subtype in ovarian carcinomas,but less common than mucinous subtype in borderline neoplasms./zML//7 promoter hypermethylation and MSI have been thought to play important roles in carcinogenesis.Molecular genetic data for ovarian mucinous cystadenocarcinoma tumorigenesis are scant.In this study,MSI at six microsatellite loci in 107 ovarian mucinous tumors(benign,borderline and malignant) was detected by microsatellite polymerase chain reaction.Hypermethylation of hMLHl promoter was assayed by restriction cut analysis,in order to investigate the role of hMLHl promoter hypermethylation in the development of ovarian mucinous tumors. MethodsOne hundred and seven of paraffin-em... |
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