Study On Methylation Of HMLH1,hMSH2Promoter In Endometriosis

Endometriosis is a common disease in young women; its incidence has risen up to10%-15%. The etiology of this disease is still not clear. Sampson's theory is the dominanttheory, as the development of immune, biochemical and genetic technology, domestic andforeign scholars put forward more new ideas, including lymph and vein spreading theory,coelomic metaplasia theory, induction theory, heredity, immune regulation and eutopicendometrium of determinism.Mismatch repair (MMR) system is an important mean for the correction of DNAreplication errors to maintain genome stability in the process of human cell proliferation. TheMMR gene changing make nucleotide incorporation and deletion in the proliferation processof the cells cannot be repaired, induce the entire genome instability and increased randommutation rate. The result is the occurrence and development of tumor with target geneschanging, such as cell growth genes, differentiation genes, apoptosis genes and tumormetastasis genes. DNA MMR system include hMSH2, hMSH3, hMSH4, hMSH5, hMSH6,hMLH1, hPMS1, hPMS2and hMLH3. The hMLH1and hMSH2are most important, and theyare responsible for the mismatch site identification and resection in gene. In DNA methylation,S-adenosylmethionine methyl groups are transferred to the fifth carbon atoms of cytosinepyrimidine ring through the DNA methyltransferase, forming the methylated cytosine.Mammals methylation occurs in the5-CPG-3sequence of the genome of cytosine, which sitewith rich CPG sequence is known as the island of CPG. in the human genome, CPG islandexists in almost half of gene transcription initiation region, and is unmethylated in the normalstate. DNA methylation and gene expression is inversely proportional; increasing of DNAmethylation can result in gene expression dropping. Many scholars had found that hMLH1and hMSH2promoter region had frequent methylation in many human malignancies, such ascolorectal cancer, gastric cancer, pancreatic cancer, bladder cancer, prostate cancer,endometrial cancer, cervical cancer and ovarian cancer. Endometriosis is a benign disease, but it has similar characteristics of malignant tumorwith recurrence and distant metastasis. In this research we studied hMLH1, hMSH2methylation and hMLH1expression in the endometriosis tissue and normal endometrial tissueby methylation specific PCR and immunohistochemistry, which showed that:(1) The low expression of hMLH1with high methylation of hMLH1promoter may be oneof the mechanisms of endometriosis.(2) The hMLH1promoter methylation and endometriosis stage are relative: hMLH1promoter methylation in III and IV type of endometriosis is significantly higher than that in Iand II. As the progresses of disease, the higher disease staging, the higher hMLH1promotermethylation.(3) Occurrence of hMSH2promoter methylation in endometriosis tissue is similar withnormal endometrial tissue.Main innovations of this study:(1) Endometriosis is benign disease, comparative study about hMLH1and hMSH2promoter methylation was done in endometriosis and normal endometrial tissue throughmethylation specific PCR, then comparative study about expression of hMLH1was done inthem through immunohistochemical method. The relationship between the hMLH1promotermethylation with expression of hMLH1.The result have enriched the endometriosis incidencetheory and provided new therapeutic approaches.(2) The hMLH1promoter methylation is found relative with endometriosis staging:hMLH1promoter methylation in III and IV type of endometriosis is significantly higher thanthat in I and II type.