Expression And Clinical Significance Of MAD2in Endometrial Carcinoma

Background Endometrial cancer is a series of epithelial malignant tumors, it usually grows in the endometrium. Adenocarcinoma which originates from the endometrial glands, is the most common endometrial cancer.. It is seen as one of the three kinds of malignant tumors in female reproductive tract, accounting for7%of the female systemic malignancy and20-30%of the female reproductive tract cancer. In recent years the morbidity is on the increase in the context of the world. The etiology in the molecular mechanisms is still unidentified. With the developments of histopathology and molecular biology, researchers have conducted a lot of studies on molecular mechanism of endometrial carcinoma from different aspects, and have made great progresses in the etiological factor of endometrial cancer. These provide the basis for the early diagnosis and treatment of patients with endometrial cancer and prolong survival of patients.According to the research of modern genetics and molecular biology, chromosomal instability (CIN) is the essential characteristics of all pre-cancerous cells and cancerous cells, which promotes neoplasia, tumor growth and heterogeneity. Chromosome separation is monitored by the system which consists of the checkpoint protein (CP). Mitotic arrest deficient2(MAD2) is one of the key components of the CP. It regulates the activity of the CP by phosphorylation and dephosphorylation in order to achieve regulation of connection between spindle microtubules and chromosome kinetochore.The abnormal expression of MAD2is considered a possible cause for neoplasia, and it is likely to become cancer diagnostic marker and therapeutic target. MAD2can perceived errors of chromosome separation by monitoring the adhesion of microtubules and feeling the pressure change. The degradation of cyclin B1is a necessary condition for cell division from medium to late until exiting mitosis.MAD2is a spindle checkpoint protein, which can be observed in the budding yeast. It plays an important role in monitoring the behavior of the mitotic spindle, and closely relates to the emergecy of CIN. MAD2expression abnormalities are found in a variety of tumor cell lines and tumor tissue, which is considered closely related to tumorigenesis. But the relationship between MAD2abnormal expression and human tumors is not very clear. In the studies of a variety of tumor cells, it is found that MAD2defects in the steady state may lead to CIN and even tumorigenesis. CIN may play an important role in the development of endometrial cancer. MAD2expression in endometrial carcinoma is barely reported at home and abroad. MAD2expression and its clinical significance for endometrial carcinoma and benign proliferative phase endometrial tissue have been studied by using immunohistochemical methods in this dissertation.Purpose Mitotic arrest deficient protein2(MAD2) is one composition of the mitotic checkpoint. It is very relevant to tumorigenesis. The study intends to clarify MAD2expression pattern in endometrial cancer, find expression differences between endometrial cancer and benign proliferative phase endometrial tissue, and analysis the clinical significance by the MAD2different expression.Methods60cases of endometrial cancer who got it during2002to2011are collected from two hospitasl, while15benign hyperplasia period patients are gathered for comparison.Their expression of MAD2protein are detected respectively by immunohistochemical methods and the relationship is sought between the MAD2protein expression and endometrial cancer which includes pathological type, tumor differentiation, hormone receptor expression, lymph node metastasis and clinical staging.Result1Immunohistochemical detection of60surgical treatment patients with endometrial cancer, MAD2high expression rate is56.7%(34/60), While it is13.3%(2/15) in the patients with benign proliferative endometrium (Figure1)(Table2).2Immunohistochemical detection of60surgical treatment patients and39lymph node excision or sampling patients with endometrial cancer,14cases have MAD2high expression in29cases without lymph node metastasis, while9cases have high expression in10cases with lymph node metastasis. The percentage of high expression is higher in patients with lymph node metastasis than not. On different staging case,12patients have MAD2high expression (total33patients in I period);7patients have high expression (total11patients in II period),14patients have high expression (total15patients in III period);1patients has high expression (total1cases in IV period). MAD2expression intensity has significantly differences (p=0.002) in the different staging of cancer tissue:the expression in the patients who are in III and IV period is significantly higher than it in I and II period (Table3). In the patients with endometrial carcinoma MAD2expression may be irrelevant to patient age, histological type, degree of histological differentiation, ER receptor expression, PR receptor expression (p>0.05). The average survival time is73.69±3.36(months) in the low expression group, and it is59.72±4.74(month) in the high expression group. The patients with higher expression of MAD2had shorter survival time,and the difference is significant (p=0.028)(Figure2). But it Is unconcerned with age, histological type and tumor cell differentiation degree.Conclusion Patient with endometrial cancer who has MAD2high expression maybe means more opportunity of lymph node metastasis, stage of late, poor prognosis, and shorter survival. It may have a positive clinical significance in guiding the postoperative adjuvant treatment and prognosis.