Detection And Clinical Significance Of Methylation Of DAB2IP In Endometrial Carcinoma Tissues

Background and ObjectiveHuman DAB2 interaction protein (hDAB2IP), a tumor suppressor gene, is a novel member of the Ras GTPase-activating protein family. It combines to the N-terminal of Dab2/DOC-2 protein, and is involved in cell signal transduction, affecting cell growth and apoptosis. It has been demonstrated to be a tumour-suppressor gene inactivated in the promoter region by methylation in several cancers.DAB2IP expression pattern has been reported in many tumor tissues and cultured cells. However, there have been none studies concerning about endometrial cancer DAB2IP expression at the protein level. In our experiment, we investigate DAB2IP protein expression pattern in endometrial carcinoma tissues by immunohistochemistry. We detect the methylation status of the promoter of DAB2IP in endometrial carcinoma tissues and normal carcinoma tissues by methylation-specific polymerase chain reaction (MSP), and explore the correlation between the methylation status of gene promoter of DAB2IP and endometrial carcinoma as well as its histopathological grading, clinical stage and lymphatic metastasis. It will also be helpful to endometrial carcinoma’s individuality therapy.Materials and MethodsEndometrial carcinoma tissues speciments (frozen tissue 30 cases and normal endometrial tissues speciments 20 cases) were collected. Then we detected the aberrant methylation of DAB2IP gene by MSP and we detected transcription level of DAB2IP gene in endometrial carcinoma tissues and normal endometrial tissues by semi-quantitative RT-PCR. Besides, we collected paraffin-embedded tissues 60 cases and detected DAB2IP protein expression pattern in endometrial carcinoma tissues by immunohistochemistry.Results(1) Immunohistochemical technology results show that compared with normal endometrium tissues, DAB2IP are very weakly expressed or even not expressed in endometrial carcinoma tissues. There is significant difference (P < 0.05).(2) Methylation rate of DAB2IP gene in endometrial carcinom tissues is 56.7% (17/30), methylation rate of DAB2IP gene in normal endometrial tissues is 0% (0/20). There is significant difference (P< 0.005).(3) Methylation rate of DAB2IP gene in the low level in clinical stage of endometrial carcinom tissues (carcinoma in situ and I) is 55% (11/20), it is lower than methylation rate (60%, 6/10) of DAB2IP gene in the high level in clinical stage of endometrial carcinom tissues (Ⅱ~Ⅳ), but there is no significant difference (P>0.05).(4) Methylation rate of DAB2IP gene in well-differentiated endometrial adenocarcinoma is 36.3% (4/11), methylation rate of DAB2IP gene moderately-poorly differentiated endometrial adenocarcinoma is 68.4% (13/19). There is no significant difference (P>0.05).(5) Methylation rate of DAB2IP gene in endometrial carcinom tissues with lymphatic metastasis is 100.0% (7/7), it is higher than methylation rate (43.4%, 10/23) of DAB2IP gene in endometrial carcinom tissues without lymphatic metastasis. There is significant difference (P<0.05).(6) Compared to unmethylation and normal endometrial adenocarcinoma, mRNA expression in adenocarcinoma tissue with DAB2IP gene promoter methylation is decreased or absent.Conclusions(1) Immunohistochemical technology results show that the expression of DAB2IP protein is down-regulated or lost in endometrial carcinom tissues. The expression of DAB2IP protein is associated with clinical stage and invasion of endometrial carcinom. However, there is no significant correlation between DAB2IP protein expression and histopathological differntiation.(2) The change of DAB2IP promoter methylation status can be detected by MSP in endometrial carcinom tissues. The aberrant promoter methylation of DAB2IP can lead to its down-regulation on mRNA level, and may partly involve in the occurrence of endometrial cancer.