The Expression Of MBD4 And Smad1 Protein And Its Clinicopathological Significance In Endometrial Endometrioid Adenocarcinoma

Objective: Endometrial carcinoma(EC) is one of the most common malignant tumor of female reproductive organs, which occurs in endometrium of uterine and accounts for about 20%-30% in female genital tract malignant tumor. In recent years,the incidence of the endometrial carcinoma are rising all over the world and it becomes the serious damage to female health. Lifestyle is closely correlated with endometrial carcinoma. The incidence of the endometrial carcinoma in various areas is different. Even in some of the developed countries such as Europe and North America, endometrial carcinoma is the leading rank of malignant tumor of female reproductive organs, following lung cancer, breast cancer and colorectal cancer. Today, an increasing incidence of endometrial carcinoma was observed in China, which is even equivalent to the cervical cancer. Endometrial carcinomas were classified into two different subtypes. Common estrogen-dependent type I(endometrial endometrioid adenocarcinoma, EEC) and rarer estrogen-independent type II are distinguished. Compared with type II, EEC has a well differentiated, good prognosis and high five-year survival rate. About 80%-90% of endometrial carcinoma is EEC.For the past several decades, the important role of the tumor suppressor genes in the generation and development of endometrial carcinoma has been recognized with the development of molecular biology.MBD4(methyl-Cp G-binding-domain 4) is a DNA mismatch repair protein, as an interactor of the mismatch repair protein MLH1, maintaining genomic stability. It is a candidate growth inhibitor in tumor and a novel tumor suppressor gene. MBD4 protein down-expression as a result of the MBD4 gene inactivation and transcription down-regulation, which would break the collectively physiological and biochemical balance, and lead to tumorigenesis, progression and metastasis. Smad1 is one of the members of Smad fimily and mediates the signals of the bone morphogenetic proteins(BMPs), which are involved in the pathway of tumor suppression. Thus, MBD4 and Smad1 are both regarded as tumor suppressor genes.This study was adopted the immunohistochemical method to test the expression of MBD4 and Smad1 in normal endometrial and EEC, furthermore, to explore the relationship of the expression between MBD4 and Smad1 in EEC preliminarily. We have analysed the relationship of MBD4 and Smad1 with age, blood pressure,blood sugar,blood lipid,FIGO stages,histologic grade,myometrial invasion and lymph nodal metastasis respectively, to further explore the occurrence and development mechanisms of the EEC.Methods: The expression of MBD4 and Smad1 was examined by immunohistochemical method in 45 normal endometrial samples and 60 samples of EEC. Six Continuous slices were obtained from each sample. Two were for immunohistochemistric staining of MBD4 and Smad1. One was for HE staining. The PBS solution was for negative control. Two was left for spare.Results:1 The expression of MBD4 in the EEC and normal endometriumThe positive rate of MBD4 expression in EEC and normal endometrium was 26.7%,60%(P=0.001), respectively. The positive rate of MBD4 protein in the EEC was obviously lower than those in the normal endometrium.2 The relation between expression of MBD4 protein and patients’ clinicopathological featuresThe results showed that MBD4 protein expression was not obviously correlated with patient’s blood pressure,blood sugar,blood lipid,FIGO stages,histologic grade,myometrial invasion and lymph nodal metastasis(P>0.05),however, MBD4 protein expression was obviously correlated with patient’s age. The positive rate of MBD4 expression in the old patients(≥55 years) and the young group(<55 years) respectively was 14.3%,44%. The positive rate of MBD4 protein expression in old patients was significantly lower than that of young ones. The difference was significantly(P=0.01).3 The expression of Smad1 in EEC and normal endometriumThe positive rate of Smad1 expression in EEC and normal endometrium respectively was 26.7%,60%(P<0.01). The positive rate of Smad1 protein expression in the EEC was obviously lower than those in the normal endometrium.4 The relation between expression of MBD4 protein and patients’ clinicopathological featuresIn endometrial endometrioid adenocarcinoma, the expression of Smad1 was not correlated with patient’s age, blood pressure, blood sugar, blood lipid, FIGO stages,myometrial invasion and lymph nodal metastasis(P>0.05), however, the Smad1 protein expression was obviously correlated with histologic grade. The difference was significantly(P<0.05). Compared with well-differentiated patients, the Smad1 expression in poorly differentiated ones was lower.5 The expression of MBD4 was positively correlated to that of Smad1 EEC(r=0.696, P<0.001).Conclusions:1 The expression of MBD4 and Smad1 protein in EEC was lower than that of normal endometrium obviously. It is prompted that the expression down-regulation of MBD4 and Smad1 protein may be associated with the occurrence of EEC.2 The expression of MBD4 in the old patients was lower than that in the young patients, it may be suggested that the down-expression of MBD4 in senescent cells increase the risk of EEC.3 The poorer tissue differentiated, the lower Smad1 protein expressed. The down-expression of Smad1 protein maybe affects prognosis of EEC.