| ObjectiveEndometrial carcinoma is now the most common pelvic genital cancer in women. It's about 7% of all female carcinoma. endometrial carcinoma threaten women healthy acutely, and its mechanism is rather complex. Modern molecular biology studies have shown that the formation and development of malignant tumors are not only associated with abnormal proliferation and differentiation, but also involved in inhibition of apoptosis, which was one of the important mechanisms in the forming of tumors. The disturbance of the modulation of apoptosis is the key link during the malignant transformation of normal endometrium. Livin is a novel human inhibitor of apoptosis protein (IAP) family member with oncogene potentiality recently discovered. Livin gene and protein express in several cell lines and tissue of tumors. The abnormal expression of livin is related with the occurrence of tumors closely. The tumor suppressor gene PTEN has been generally acknowledged, and recent research show it inhibit tumor mainly by increase apoptosis, PTEN protein regulate growth and proliferation of cells by repressing of PI3K/Akt signal transduction pathway.In order to investigate the possible mechanism of livin, PTEN, PI3K in the endometrial carcinoma, The expressions of livin, PTEN, PI3K in tissues from endometrial adenocarcinoma, simple endometrial hyperplasia, endometrial atypical hyperplasia, and normal endometrium were detected by using S-P immunohistochemistry stain, western blot and reverse transcription polymerase chain reaction.Methods1. PatientsIn this study, the samples were chosen from benign and malignant endometrium 58 cases who suffered from hysterectomy at the Department of Gynecology and Obstetrics, Shenjing Hospital of China Medical University, from 2003-1 to 2006-4. They had been diagnosised correctly by routine pathological examination. None of the patients had received radiotherapy, chemotherapy, hormonal therapy and other treatment before operation. The full clinical data had been collected. The range of year from 31Y to 74Y. These 58 cases of specimens included endometrial adencarcinoma, endometrial atypical hyperplasia, and normal endometrium.2. MethodsThe expressions of livin, PTEN, PI3K protein in tissues from 36 cases of endometrial adenocarcinoma, 12 endometrial atypical hyperplasia, and 10 normal endometrium were detected by using immunohistochemistry S-P method and image analysis system. The contents of livinα, livinβ, PTEN, PI3K protein in tissues from 36 cases of endometrial adenocarcinoma, 12 endometrial atypical hyperplasia, and 10 normal endometrium were detected by using western blot. The contents of livinαmRNA and livinβmRNA in tissues from 36 cases of endometrial adenocarcinoma, 12 endometrial atypical hyperplasia, and 10 normal endometrium were detected by using RT-PCR.3. Statistical AnalysisSPSS 11.5 software was employed to analyze all data. Statistical evaluation was performed using One Way ANOVA, Independent-Samples T test, Spearman's test. P＜0.05 was considered as statistical significance.Results1. The expressions of livin protein and mRNA in the tissues of normal endometrium, endometrial carcinoma and precancerous lesion. In the immunohistochemistry stain, livin protein maily restricted to cytoplasm, and less was restricted to nucleus. Being compared with normal endometrium, the expression of livin protein in the cases of atypical hyperplasia and carcinoma was significantly up-regulation (F=41.052, P＜0.001). The results of western blot and RT-PCR were according to the immunohistochemistry stain, livin protein and mRNA were only expressed in the malignant endometrium, especially in adenocarcinoma, but shows little or no expression in benign tissue. There was significantly difference between different patholigical grade and muscular invasion depth (P＜0.001), the expression of livin has no significant difference with clinical stage. The expression of livinβwas significantly higher than livinαin the same type of tissue(P＜0.001).2. The expressions of PTEN protein in the tissues of normal endometrium, endometrial carcinoma and precancerous lesion. In the immunohistochemistry stain, PTEN protein maily restricted to cytoplasm, and less was restricted to nucleus. Being compared with normal endometrium, the expression of PTEN protein in the cases of atypical hyperplasia and carcinoma was significantly down-regulation (F=33.34, P＜0.001). The results of western blot were according to the immunohistochemistry stain, there was significantly difference between different patholigical grade (F=31.38, P＜0.001), the expression of PTEN has no significant difference with clinical stage and muscular invasion depth(P＞0.05).3. The expressions of PI3K protein in the tissues of normal endometrium, endometrial carcinoma and precancerous lesion. In the immunohistochemistry stain, PI3K protein only restricted to cytoplasm. Being compared with normal endometrium, the expression of PI3K protein in the cases of atypical hyperplasia and carcinoma was significantly up-regulation (F=56.31, P＜0.001). The results of western blot were according to the immunohistochemistry stain, there was significantly difference between different patholigical grade (F=31.38, P＜0.001), the expression of PI3K has no significant difference with clinical stage nd muscular invasion depth(P＞0.05).4. Negative correlations were observed between the expression of livin and PTEN (livinα:r=0.748, P＜0.001; livinβ:r=0.721, P＜0.001); Negative correlations were observed between the expression of PTEN and PI3K (r=0.711, P＜0.001).Conclusions 1. livin was only expressed in the endometrial carcinoma and precancerous lesion, especially in adenocarcinoma, bur shows little or no expression in benign endometrium. The expression of livin was closely related to patholigical grade and muscular invasion depth, which could be tunor marker and to evaluate prognosis in endometrial carcinoma. Livinβmay play more important role than livinαin endometrial carcinoma.2. The low expression of PTEN was closely related to pathological grades, and in the atypical hyperplasia that the expression of PTEN is decreased. It suppress the loss of PTEN protein may be an early event in the development of endomrtrial carcinoma.3. The high expression of PI3K in endometrial carcinoma was related to pathological grades. and may participate in the occurrence and development of endometrial carcinoma.4. The loss of PTEN resulted in the activation of PI3K/Akt signal transduction pathway, the expression of livin was up-regulate, then the cell cycle was stated, apoptosis was restrainted. These three factors promoted the development of endometrial carcinoma.
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