A Study On The Mutations Of HMSH₂,hMLH₁ In Endometrial Carcinoma Tissue

Objective: To explore associations between mutations of mismatch repair gene hMSH2, hMLH₁ and clinicopathological characteristics of endometrial carcinomas. To discuss the role of the mutation of hMSH2, hMLHi in hereditary and sporadic endometrial carcinomas and the relationship between mutation of hMSH₂ and hMLHi.Methods: We measured mutations of hMSH₂ and hMLHi genes in 61 endometrial carcinoma tissues (13 hereditary endometrial carcinomas , 14 aspecific cancer aggregates endometrial carcinoma and 34 sporadic endometrial carcinomas according to Amsterdam Criteria II ), 12 atypical hyperplasia and 35 healthy individuals (18 normal secretory endometriums and 17 normal proliferative endometriums) by PCR—SSCP. The relationship between the germline mutations of hMSH₂ and hMLHi and clinicopathologic characteristics of endometrial carcinoma and hereditary endometrial carcinoma were analyzed.Result:1. Mutations of the hMSH₂ and hMLHi genes was found in 18.0% and 16.4% endometrial carcinoma respectively, whereas none of normal endometrium. Mutations of hMSH₂ and hMLHi genes in endometrial carcinoma and atypical hyperplasia was higher than that in normal endometrium (P=0.008, P=0.010). There was no statistic different between cancer and atypical hyperplasia in mutations of the two genes, also between atypical hyperplasia and normal endometrium in mutation of hMSH₂.2.11 cases of hMSH₂ mutation exist in exonl (2) , 3, 11, 12, 13 (3), 15 (2) and 16 respectively. 11 cases of hMLHi mutation exist in exonl% 11% 12% 13 (2) , 15, 16, 17 (2), 19 respectively.3. There was no relationship between mutations of hMSH₂ , hMLH₁ genes and age, menopause, diabetes mellitus, hypertension, multiple primary cancers, cancerhistory, histological types, FIGO stage, myometrial invasion, grades, lymphonode metastase.4. The mutations of hMSFfe and hMLHi is higher in hereditary endometrial carcinoma than that in normal endometrium (P=0.000, P=0.005). The mutations of hMSEfe is higher in aspecific cancer aggregates carcinoma than that in normal endometrium(P=0.035).There was no statistic different between hereditary and aspecific cancer aggregates endometrial carcinoma in mutation of two genes, also between aspecific cancer aggregates carcinoma and normal endometrium in mutation of hMLHi.5. There was significant correlation between mutations of I1MSH2 and hMLHi genes.Conclusions:1. Mutations of the hMSH2 and hMLHi genes was found endometrial carcinoma, whereas none of atypical hyperplasia and normal endometrium. Mutations of I1MSH2 and hMLHi genes in endometrial carcinoma and atypical hyperplasia were higher than that in normal endometrium. There was no statistic different between cancer and atypical hyperplasia in mutations of the two genes, also between atypical hyperplasia and normal endometrium in mutation of I1MSH2. It is therefore presumed that mutations of I1MSH2 and hMLHi were related to the early onset of endometrial carcinoma.2.11 cases of hMSH2 mutation exist in exonl (2) > 3n 11% 12^ 13 (3) -. 15 (2) and 16 respectively. 11 cases of hMLHi mutation exist in exonl> 11n 12> 13 (2) ^ 15^ 16> 17 (2) > 19 respectively. It was suggested that mutations of hMSH2 and hMLHi existed in exon after 10.3. There was no relationship between mutations of hMSH2 > hMLHi genes and age, menopause, diabetes mellitus, hypertension, multiple primary cancers, cancer history, histological types, FIGO stage, myometrial invasion, grades, lymphonodemetastase.4. The mutations of hMSH2 and hMLHi is higher in hereditary endometrial carcinoma than that in normal endometrium. The mutations of hMSFk is higher in aspecific cancer aggregates carcinoma than that in normal endometrium.There was no statistic different between hereditary and aspecific cancer aggregates endometrial carcinoma in mutation of two genes, also between aspecific cancer aggregates carcinoma and normal endometrium in mutation of hMLHi. It is therefore presumed that I1MSH2 and hMLHi play an important role in the onset of hereditary hereditary and aspecific cancer aggregates endometrial carcinoma.5. There was significant correlation between mutations of I1MSH2 and hMLHi genes. Which suggest mutation occurs in either I1MSH2 or hMLHi, and possibly result in loss of ability of MMR gene mismatch repair.