A Study Of MUC1 Expression In Endometrial Adenocarcinoma And The Correlation With ER And PR Expression

Background and Objective:Endometrial carcinoma (EMC) is a malignant disease which derives from endometrium, most of which is adenocarcinoma. It is one of the most common malignant tumors in department of gynecology.This disease has seriously threatened the women's health.Now,its molecular mechanism has not been made clear,wile the key to the prevention and treatment of this disease is to make clear the causes and mechanisms of this disease. So it is of great significnce to explore the molecular mechanism of the disease and new way of treatment.Mucin1(MUC1)-a memember of the mucin family,is type I transmembrane protein.It is a multi-functional molecules, such as participation in the protection of cell surface structure, the release of active molecules involved in signal transduction and the occurrence,development,invasion and metastasis of turner,etc,which has take more and more attention of scholars in recent years. It have been reported in lot's of literature at home and abroad that MUC1 over-expressed in breast cancer, ovarian cancer etc and is related to the invasion and metastasis of these tumor mentioned above. Because of its unique immunological characteristics, and the abnormal expression in tumor tissues, MUC1 is an ideal target molecule for tumor active specific immunotherapy. A variety of MUC1-based vaccine have been developed for tumor biological therapy at home and abroad, such as peptides vaccines, DNA vaccines, some of which have entered clinical trials.There is very little report about the expression of MUC1 in endometrial carcinoma and no report about the MUC1 expression and its relationship with clinical and pathological features of endometrial cancer has been found in domestic and abroad.So,in this study,we used immunohistochemical method to detect MUC1 expression in different endometrial tissues, and its relationship with surgery-pathological stage, pathological grade, myometrial invasion, lymph node metastasis and ER, PR expression in order to investigate its role in the occurrence and development of endometrial cancer and to provide a new theoretical basis of the diagnosis of endometrial cancer and the exploration of new avenues of treatment to this disease.Materials and Methods:1. Source of specimen:The 58 cases of endometrial carcinoma 20 cases of atypical hyperplasia endomembrane, and 20 cases of estrin phase endomembrane came from archived wax blocks collected from January 2005～April 2008 stored in the department of pathology of First Affiliated Hospital of Zhengzhou University. The 98 cases of patients, aged from 38 to 78 years old, the average age of which was 54.8±5.6 years old. The 58 cases of endometrial carcinoma included 31 cases of clinical stageⅠ,19 cases of stageⅡ, and 8 cases of stageⅢ,0 cases of stageIV by FIGO surgery-pathology stage in 2000;22 cases of well differentiated,27 cases of moderately differentiated, and 9 cases of poorly differentiated by FIGO histology-pathology stage in 1988; 35 cases of superficial myometrial invasion(≤1/2) and 23 cases of deep myometrial invasion(>1/2); 6 cases of lymph node metastasis and 52 cases of no lymph node metastasis. None of these patients were given preoperative radiotherapy, chemotherapy and hormone treatment.2. Methods:Immunohistochemistry SP was used to detect the expression of MUC1 in 20 cases of normal endometrial in proliferative phase,20 cases of atypical hyperplasia and 58 cases of endometrial carcinoma.The correlation of MUC1 expression and clinical and pathological parameters and ER, PR expression in endometrial carcinoma group were also analysed.All datas were treated by the SPSS statistical package program 13.0, x test, Fisher's exact probability method were used to analyse the expression of mucin MUC1 in three groups of endometrial tissue and relationship between MUC1 expression and the clinicopathological parameters of endometrial carcinoma. Spearman rank correlation analysis was used to analyze the relationship between the MUC1 and ER, PR protein expression in endometrial carcinoma.The statistically significant level wasα=0.05.Results:1. The positive rate of MUC1 in endometrial carcinoma group and atypical hyperplasia group were 46.6%(27/58) and 35.0%(7/20),much higher than that in normal proliferative endometrial group (5%,4/20), where the difference was statistically significant (χ2=11.189, P<0.05).2. In endometrial carcinoma group the positive rate of MUC1 in FIGO stageⅡ-Ⅲ(66.7%,18/27)and deep myometrial invasion (78.3%,18/23) and positive lymph meststases(100%,6/6),were much higher than that in stageⅠ(29.0%,9/31) (χ2=8.215,P<0.05) and superficial myometrial invasion and negative lymph meststases (40.4%,21/52)(Fisher,s exact probability method,P=0.007).3. In endometrial carcinoma group, the positive rate of ER and PR was respectively 56.9%(33/58) and 63.8%(37/58).The positive rate of ER in FIGO stage I (77.4%,24/31) and superficial myometrial invasion(82.9%,29/35) and negative lymph meststases(63.5%,33/52)and well differentiated (77.3.0%,17/22) were much higher than that in stageⅡ-Ⅲ(33.3%,9/21)(χ2=11.437, P<0.05) and negative lymph meststases(63.5%,33/52) and superficial myometrial invasion(82.9%,29/35) and moderately-poorly differentiated (44.4%,16/36)(χ2=6.001,P<0.05).The positive rate of PR in FIGO stageⅠ83.9%(26/31) and negative lymph meststases(69.2%,36/52) and superficial myometrial invasion (88.6%,31/35) and well differentiated (86.4%,19/22) much higher than that in stageⅡ-Ⅲ(40.7%, 11/27)(χ2=11.622,P<0.05) and positive lymph meststases(16.7%,1/6)(P=0.02,Fisher's exact probability method) and deep myometrial invasion (88.6%,31/35)(P=0.000,Fisher's exact probability method) and moderately-poorly differentiated(50.0%,18/36) (χ2=7.817,P<0.05).4. The relationship between MUC1 and ER,PR:In the 58 cases of endometrium carcinoma, the syn-positive and syn-negtive expression of MUC1 and ER was 18 cases and 16 cases respectively. There was no statistically significant difference,by Spearman correlation analysis(r=0.184, P=0.166, greater than 0.05)which means that there was no statistically significant correlation between MUC1 expression and the expression of ER.The syn-positive and syn-negtive expression of MUC1 and PR was 10 cases and 4 case respectively. There difference was statistically significant, by Spearman correlation analysis(r=-0.520, P=0.000) which means that there was a negative correlation between MUC1 expression and the expression of PR.Conclusions:1. With the progress of endometrial tissue lesions,from proliferation to endometrial cancer,the trend of MUC1 expression was increasig;In endometrial carcinoma MUC1 more commonly expressed in cases of late surgical-pathologic stage, deep myometrial invasion and positive lymph node metastasis.These indicated that MUC1 was involved in the genesis and development of endometrial cancer and may be related to invasion and metastasis of this disease.2. MUC1 expression was negatively correlated with PR expression in endometrial carcinoma and had no significant correlation with ER expression which shows that negative regulation may exist between MUC1 and PR expression in the occurrence and development of endometrial cancer.