Expressions Of MDM2, Livin And Caspase-3 Protein And MRNA In Endometrioid Adenocarcinoma And Their Significance

Objective To detect the protein and mRNA expression of inhibitor of murine double mimute2 (MDM2), Inhibitor of apoptosis protein (Livin) and cysteinyl aspartate-specific proteinases (Caspase-3) in tissues from endometrioid adenocarcinoma, endometrial hyperplasia and normal endometrium.To investigate their roles in carcinogenesis, biological behavior and to evaluate their clinicopathologic significance. Methods The expression levels of MDM2, Livin and Caspase-3proteins and mRNA in endometrioid adenocarcinoma tissues (n=72), endometrial hyperplasia tissues (n=60) and normal tissues (n=30) were examined by immunohistochemistry and in situ hybridization method. Results 1. The positive rates of MDM2, Livin and Caspase-3protein and mRNA in endometrioid adenocarcinoma were respectively 80.6% (58/72), 80.6% (58/72), 33.3% (24/72), 73.6% (53/72), 75.0% (54/72), 27.8% (20/72). 2. The positive rates of MDM2 and Livin protein and mRNA in endometrioid adenocarcinoma tissues were significantly higher than that in normal endometrium and endometrial hyperplasia (P<0.05), and the positive rates of MDM2 protein and mRNA in Complex endometrial hyperplasia with atypical were significantly higher than that in normal endometrium. The positive expression of MDM2 was not related to the histological grade, FIGO stage, depth of invasion and lymph node metastasis. The positive expression of Livin was related to histological grade (P<0.01), but it was not related to FIGO stage, depth of invasion and the lymph node metastasis. 3.The protein and mRNA expression of Caspase-3 was significantly weak in Complex endometrial hyperplasia with atypical as well as endometrioid adenocarcinoma tissues. The positive expression of Caspase-3 was correlated to histological grade (P<0.05), but it was not correlated to FIGO stage, depth of invasion and the lymph node metastasis. 4. The expressions of MDM2, Livin and Caspase-3 protein were positively correlated their mRNA. The expression of Livin was negatively correlated Caspase-3. The expression of MDM2 was not found to be correlated with both Livin and Caspase-3. Conclusion 1. The expression of MDM2 was upregulated in Complex endometrial hyperplasia with atypical as well as endometrioid adenocarcinoma tissues, implying that MDM2 was activated in the early stage of endometrioid adenocarcinoma. 2. The expression of Livin in endometrioid adenocarcinoma was higher than that in normal endometrium and endometrial hyperplasia, which prevented cell differentiation and promoted cell proliferation and associated with the development and progression of endometrioid adenocarcinoma. 3. The expression of MDM2 in normal endometrium was higher than that in both endometrioid adenocarcinoma and Complex endometrial hyperplasia with atypical, which was negatively correlated to the histological grade. The repression of apoptosis which was caused by degraded expression of Caspase-3 stimulated cell proliferation abnormally by the way of avoiding cell death and joined in the whole process of the occurrence and development of endometrioid adenocarcinoma 4. MDM2, Livin and Caspase-3 gene varied in the development and progression of endometrioid adenocarcinoma. They may be a important biomarker to diagnose the early carcinogenesis and metastasis of endometrioid adenocarcinoma and to come up with direction in the targeted therapy.