The Expression And Clinicopathological Significance Of MBD4 And KISS-1 Protein In Endometrial Endometrioid Adenocarcinoma

Objective: Endometrial cancers(Endometrial Carcinoma) is one of the three malignant tumors of female genital tract,compared with 20% ~ 30%, and 7% of female malignant tumors.The prevalence of endometrial cancer has significantly increased year by year in the world during the past several decades.About 74000 women died each year from endometrial cancer, mainly because of the recurrence and metastasis of cancer.Endometrial endometrioid adenocarcinoma(EEC) is the major histological type of endometrial cancer and there is a great need for better markers with high sensitivity and specificity to permit early diagnosis and indicate prognosis of EEC.The occurrence and development of tumor is the common effect of the external environment and the body’s own situation,furthermore,it can not be ignored that the genetic factors of the body play an important role.Epigenetic alterations in cancers are a new field and the methylation of DNA has emerged as a most critical player in epigenetic mechanisms.Epigenetic gene inactivation through Cp G promoter hypermethylation was an important aberration involved in the silencing of tumor suppressor gene,which has been shown to play an important role in tumorigenesis.The methyl-Cp G binding domain 4(MBD4),also known as MED1,was recognized as a mediator of cell cycle arrest and apoptosis,and play a central role in suppression of Cp G mutability and tumorigenesis.MBD4 has been reported to be a candidate tumor suppressor gene in esophageal squamous cell carcinoma and lung cancer.However,there were few reports about its possible role in endometrial endometrioid adenocarcinoma yet.The invasion and metastasis of tumor is an extremely complex process that remains to be a major problem in the management of cancer.Ki SS-1 gene was discovered in metastasis-suppressed melanoma and recently known to strongly respond to tumor cell invasion suppression.In the present,intensive investigations have provided substantial evidence suggesting roles of the KISS-1 in the suppression of metastasis with a variety of cancers except EEC.Therefore,this study adopted the method of immunohistochemical,testing the expression of MBD4 and KISS-1 in normal endometrium and endometrioid adenocarcinoma,to preliminary discuss their roles in the occurrence and development of EEC and relationships with clinicopathological factors.Methods: The expression of MBD4 and KISS-1 was examined by SP immunohistochemical method in 45 normal endometrial(NE) samples and 60 samples of EEC.Six continuous slices were obtained from each sample.Two were for immunohistochemistric staining of MBD4 and KISS-1.Two was for HE staining and negative control.Two was left for spare.The PBS solution was chosen for negative control.Results:1 The expression of MBD4 in NE and EEC.MBD4 protein was expressed in the nucleus and cytoplasm of endometrial glandular cells.MBD4 protein was positively expressed in 16 tumors from 60 tumors.The positive rate of MBD4 protein in EEC was 27%.MBD4 protein positively expressed in 27 normal endometriums from 60 normal endometriums.The positive rate of MBD4 protein in normal endometrium was 60%,siginificantly higher than 27% of normal endometrium(P<0.05).2 The relation between expression of MBD4 protein and patients’ clinical pathological features.The results showed that MBD4 protein expression was not obviously correlated with patient’s blood pressure,blood lipid,blood sugar,FIGO stages,histologic grade,myometrial invasion,estrogen exposure time and lymph nodal metastasis(P>0.05).The expression of MBD4 protein was obviously correlated with patient’s age.The rate of positive expression of MBD4 protein in young patients was significantly higher than that of old ones(P<0.05).3 KISS-1 expression in NE and EEC.KISS-1 protein was expressed mainly in the cytoplasm.KISS-1 protein positively expressed in 13 tumors from 60 tumors.The positive rate of KISS-1 protein in EEC was 22%. KISS-1 protein positively expressed in 35 normal endometriums from 60 normal endometriums.The positive rate of KISS-1 protein in normal endometrium was 78%,siginificantly higher than 22% of EEC(P<0.05).4 The relation between expression of KISS-1 protein and patients’ clinicopathological features.The results showed that KISS-1 protein expression was not obviously correlated with patient’s blood pressure,blood lipid,blood sugar,histologic grade,lymph nodal metastasis,estrogen exposure time and age(P>0.05).But KISS-1 protein expression was obviously correlated with patient’s clinic stages and myometrial invasion.The difference of them was significantly(P<0.05).Ki SS-1 expression was significantly lower in cases of advanced stage and deeper myometrial invasion.Conclusions:1 Immunohistochemical staining showed that expression of MBD4 protein were significantly higher in normal endometrium than that in EEC.The results showed that MBD4 protein may could inhibit the occurrence of EEC.2 MBD4 protein abnormalities may not be a late event in endometrial endometrioid adenocarcinoma.The rate of MBD4 protein positive expression in young patients was significantly higher than that of old ones.We can assume that the down-expression of MBD4 protein may be associated with the growth of age.3 The expression of KISS-1 protein were significantly higher in normal endometrium than that in EEC,suggesting that KISS-1 protein expression was down-regulated in the occurrence of EEC.4 KISS-1 protein expression was obviously correlated with patient’s FIGO stages and deep myometrial invasion.The down-expression of Ki SS-1 is more often in the process of progressing to metastases of EEC,suggesting it may be a new biomarker in the process of metastasis of EEC.