| [Purpose] The expression of hMLH 1, hMSH2, hMSH6, and hPMS2 was detected in endometrial carcinoma tissue by immunohistochemistry, and investigated the role of DNA mismatch repair (MMR) gene in the development of endometrial carcinoma, so as to provide a more effective objective indicator for the early detected potentially high-risk patient groups and evaluate prognosis. In order to analyze the clinicopathological characteristics and prognosis of Lynch syndrome associated endometrial cancer, Explore the immunohistochemical is used to detect the MMR protein’s expression situation’s role in the early-term detection screening of the role of endometrial cancer patients and their family., and early detection of Lynch syndrome patients will be conducive to other family members’early intervention, and then it will reduce the morbidity and mortality of Lynch syndrome related tumor.[Method] This study is about the retrospective analysis of 176 examples endometrial carcinoma patients’ onset age, clinical pathological characteristics, treatment and prognosis,using immunohistochemical SP method to detect 135 examples of endometrial carcinoma tissue’s(endometrial carcinoma group, including 128 cases of sporadic endometrial carcinoma,18 cases of Lynch syndrome related endometrial carcinoma 30 cases of nonspecific tumor aggregation endometrial carcinoma) expression of hMLHl,hMSH2, hMSH6 and hPMS2, and select 15 cases of atypical hyperplasia endometrial tissue(hyperplasia group, including simple and complex atypical hyperplasia),20 cases of normal cycle endometrial tissue(normal group, the endometrium of hysteromyoma hysterectomy specimen)as the control group, and analysis the expression characters of these four indicators in control group and endometrial carcinoma;and analyze 18 Lynch syndrome related EC cases,30 nonspecific tumor aggregation EC patients and 87 sporadic EC cases’ clinical pathological features and prognosis’ differences and the expression of the above four MMR protein indicators. Followed-up 135 cases of endometrial carcinoma patients.Mainly research 18 patients with endometrial cancer conforms to the Amsterdam Criteria II(AC II)diagnostic criteria and 3 cases of Lynch syndrome family in line with the diagnostic criteria. Review and study the Lynch syndrome’s related endometrial cancer incidence and attack risk, clinical pathology characteristics, the characteristics and test method of molecular biology, screening criteria and prevention methods, etc.; Use SPSS 17.0 statistical software to deal with the data of experimental resule. x2 test, Fisherman exact probability test, Spearman are used to do statistical analysis, and P< 0.05 indicates the difference has statistically significant.[Result] 1.176 cases of endometrial carcinoma tissue are devided according to the pathology classification, with 93(52.48%) belong to the G1 stage,83(47.16%)belong to G2-G3. According to the pathological type of classification,162 cases of endometrial adenocarcinoma account for 92.05%,10 cases of serous papillary adenocarcinoma account for 5.68%, and 4 cases of clear cell carcinoma account for 2.27%.Among the 176 cases, there are 18 cases with nomyometrium invasion, accounting for 10.23%, there are 116 cases of myometrium invasion≤1/2, accounting for 65.91%, and there are 42 cases of myometrium invasion> 1/2, accounting for 23.86%.There are 32 cases of lymph node metastasis, accounting for 18.18%, and 144 cases with no lymph node metastasis, accounting for 81.82%.And among the 135 follow-up cases,110 cases survived, accounting for 81.48%, and 25 dead cases, accounting for 18.52%.2. According to the HNPCC revised criteria for the diagnosis made by international HNPCC consortium in 1998, the 176 EC patients can be divided into:First division, 128 sporadic endometiral carcinoma with no family history of malignant tumor; nonspecific tumor gathered endometrial carcinoma with 2-3 family members in 1-2 generation having different types of maligant tumors, but this is not in conformity with the 30 cases of diagnostic criteria of HNPCC.The third group,18 cases of HNPCC related endometrial carcinoma according to the revised diagnostic criteria.3.Follow-up resultUntil June 30,2014,135 had been followed up, a total of 124 cases were survival, accounting for 91.85%, of which 110 cases survived more than 5 years, accounting for 81.48%;There were 25 death cases, accounting for 18.52%, including 21 cases died of tumor, accounting for 84%. There were other reasons (including heart failure, renal failure,cerebral hemorrhage),4 cases of death, accounting for 16%(4/25).The first group has 17 death patients, and the survival rate is 86.72%. In the second group,6 cases of death, and the survival rate is 80%; In the third group, there are 2 dea的 cases,and the survival rate was 88.89%. There are no significant differences in the prognosis of the 3 groups’patienrs(x2=0.635, P=0.804).7 cases in the first group,4 cases in the second group, and 5 cases in the third group, all were complicated with the tumor of other organ. The three groups were complicated with the tumor of other parts have statistically significance (x2=8.951, P=0.007), so were the third group and the first group (P<0.05), and the third group and the second group (P>0.05).4.The expression of hMLHl, hMSH2, hMSH6 and hPMS24.1 At least one deletion rate of hMLHl and hMSH2, hMSH6 and hPMS2 of hyperplasia group, endometrial carcinoma group and normal group is 26.67%(4/15), 34.81%(47/135),O. Hyperplasia group and endometrial carcinoma group has no significant difference, but both were significantly higher than that of normal group, P <0.05).4.2 The expression differences of hMLHl and hMSH2, hMSH6 and hPMS2 in different age group of endometrial carcinoma.In the endometrial carcinoma group, the MMR deletion rate of people who is younger than 45, who is between45～60-year-old,who is older than 60,is54.17%、34.07% and 15%.There is a difference between the MMR protein deletion rate of people younger than 45 and older than 60, P<0.05.4.3 The relation between the clinical pathological indicators and expression of hMLH1、hMSH2、hMSH6 and hPMS2 Of 135 endometrial cancer examples’ hMLH1, hPMS2, hMSH2 and hMSH6’s expression in Gl is 18.28%,13.98%,16.13%,13.98% respectively, and in the G2 G3, the data is 16.87%,12.05%,10.84%,12.05%, and the two groups’ MMR protein expressions have no difference (x2= 0.917, P= 0.917). The above data shows that the MMR expression is not related to the patients’ pathological staging.4.4 The expression of hMLH1、hMS2、hMSH6 and hPMS2 in the first, second and third group.The 1st group including 87 cases of sporadic endometrial cancer MMR deletion rate is 22.99%(20/87),the second group including 30 nonspecific tumor gathered endometrial cancer patients’ MMR deletion. Rate is 36.67%(11/30),and the third group’s 18 Lynch syndrome related endometrial cancer patients’ MMR deletion rate is88.89%(16/18).The MMR deletion rate of the third group is obviously higher than that of the first group, and the difference has its statistically significant(x2=9.479, P=0.001).The MMR deletion rate is different among the patients of three groups(x2=10.221, P=0.006)。 The third group’s and second group’s MMR protein have no difference(x2=3.301, P=0.058)。[Conclusion] 1.Expression of MMR gene protein decreases gradually in normal group, hyperplasia group and endocarcinoma group. Difference in deletion rate of 4 MMR gene proteins in hyperplasia group and endocarcinoma group is not statistically significant, however both of them are higher than normal group, indicating MMR gene mutation can happen even in atypical hyperplasia phase of endometria due to poor biological behavior. Combination test of multiple MMR gene protein can be an additional biomarker to help diagnosis of atypical hyperplasia so as to early identify patient with higher malignant potential.2.In patients with EC, the highest mutation MMR gene is hMLHl, followed by hMSH2. In patients with LS-associated EC, mutation rate of hMSH6 is higher than hMSH2. Deletion rate of MMR gene in younger patient is 54.71%, which is 15% higher than older patients. However, there is no relation of MMR gene expression and clinical pathological stage.3.LS-related EC has an earlier average age of onset, and tends to have combined neoplasm of other body organ systems. Histology expression includes adenocarcinoma, higher degree of cell differentiation, and better prognosis. In younger patient who has combined neoplasm of other body organ system simultaneously or after diagnosis of EC, or malignant neoplasms happen in his/her family, LS should be highly suspicious if there is deletion of MMR gene, and the whole pedigree should be investigated.4. By immunohistochemistry method to test of MMR protein and combined with clinical data is helpful in early detection of Lynch syndrome patients and their pedigree. |
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