The Loss Expression Of Arid1a In Endometrial Carcinoma And Its Correlation With ER, PR, GR, HIF-1a, VEGF

Objective: Endometrial cancer is a common malignant tumor of femalegenital systerm, which is ascending year by year. In the past20years, thebasic and clinical researches on endometrial cancer have also made a lot ofprogress. Currently, the occurrence of endometrial cancer is correlated with avariety of factors, especially with long-term estrogen stimulation withoutantagonist-related progesterone generally recognized. But the tumorgencity ofendometrial carcinoma is still not clear. Chromatin-remodelling complexes areone of popular territory in molecalar organism and cytobiology that playfundamental roles in genetic transcription, recombination, replication of DNAand reparation, and play important roles in the process of the development oftumors. ARID1a is a subunit of human SWI/SNF-relatedchromatin-remodelling complexes and be thought as a new tumor suppressorgene. Among759kinds of maligant tumors, ARID1a gene mutations werefound in6%of these tumors. Currently the investigation about ARID1a ismostly concentrated on its genetic structure analysis. However, the mechanismabout loss expression of ARID1a in tumors and the functions of ARID1a astumor-suppressing gene have been rarely reported. Here we analysis theexpression of ARID1a and its correlation with ER, PR, GR, HIF-1a and VEGFin endometrial cancer, trying to find that the relations between the lossexpression of ARID1a and the occurrence of endometrial carcinoma.Methods:1The expression level of ARID1a, GR, HIF-1a, VEGF, ER and PRmRNA in endometrial cancer and normal endometrium were detected byRT-PCR.2Immunohistochemistry methods were used to detect ARID1a, ER, PR,GR, HIF-1a and VEGF protein in paraffin-embedded specimens, including30 samples of I type endometrial carcinoma (10with high-grade,10withmiddle-grade and10with low-grade endometrioid cancer,respectively),30samples of II endometrial cancer (10was clear cell carcinoma,10wassmall-cell carcinoma,7was serous caecinoma),10samples of complexityendometrial hyperplasia,5samples of atypia hyperplasia,10samples ofnormal endometrial tissue.3The correlation of the ARID1a with the exppressions of GR, HIF-1a,VEGF, ER and PR in endometrial cancer were evaluated by Chi-square testand t test, and the relationship of these factors was analyzde by Spearman rankcorrelation test.Results：1Compared with the expression level of ARID1a, ER, PR, GR, HIF-1aand VEGF in normal endometrial tissue, the expression levels of ARID1a, ERand PR mRNA in endometrial carcinoma tissue were gradually decreased(P<0.05). In contrast, the expression level of GR, HIF-1a and VEGF mRNAin endometrial carcinoma tissue was significantly increased than those innormal endometrial tissue (P<0.05).2The expression level of ARID1a mRNA in high-grade endometrialcarcinoma was gradually increased than that in moderate-grade and low-grade(P<0.05), there was a negative correlation between ARID1a and pathologicalgrading of endometrioid cancer (r=-0.527).3The high expression of BAF250a was found in normal endometriumtissues, complexity hyperplasia endometrial tissues and atypia hyperplasiatissues. The expressions of BAF250a and ER were much lower in endometrialadenocarcinoma than in normal endometrium (P<0.05). However, theexpressions of GR, HIF-1a and VEGF protein were much higher inendometrial adenocarcinoma than in normal endometrium (P<0.05).4The expression level of BAF250a protein in high-grade endometrialcarcinoma was gradually increased than that in moderate-grade and low-grade(P<0.05), there was a negative correlation of BAF250a with pathologicalgrading of endometrial carcinoma (P<0.05, r=-0.836), but no correlation of BAF250a with clinical stage and the depth of tumor was found in endometrialcarcinoma (P>0.05).5The loss expression rate of BAF250a in poor differentiationendometrial adenocarcinoma and endometrial clear cell carcinoma was40%and30%, respectively.6There was no significant correlation of ARID1a with GR, HIF-1a,VEGF and PR protein (P>0.05). However, in the poor-differentiatedendometrial adenocarcinoma, there was a positive correlation of BAF250awith ER. The expressions of VEGF and HIF-1a have positively correlatedwith each other. Moreover, the expressions of HIF-1a and VEGF werepositively correlated with ER in endometrial andenocarcinoma.7In the endometrial adenocarcinoma, there was negative correlation ofBAF250a expression with mutated P53gene expression (P=0.035, r=-2.274).Conclusion:1The expression of ARID1a mRNA and protein was much lower inendometrial carcinoma than in normal endometrial tissue indicating thatARID1a may play an important role in the carcinogenesis of endometrialcarcinoma.2ARID1a mRNA and protein expression is correlated with pathologicalgrading of endometrial carcinoma. The loss of ARID1a expression was foundmore frequently in poor differentiation endometrial carcinoma and clear cellcarcinoma than that in high differentiation endometrial carcinoma and uterineserous adenocarcinoma, which showed that ARID1a may be correlated withthe special category of endometrial cancer.3The expression of HIF-1a and VEGF was correlatted with ER, whichindicated that HIF-1a and VEGF might be affcted by estrogen in endometrialcancer. In addition, the expression of VEGF and HIF-1a had positivecorrelation in endometrial cancer indicating that HIF-1a may upregulate thetarget gene VEGF to promote the generation of blood vessels in tumor tissue,which contributes to the development of tumor invasion and metastasis.4In the poor-differentiated endometrial adenocarcinoma, there was positive correlation of BAF250a with ER, and the expressions of HIF-1a andVEGF were also correlatted with ER, showing that the loss expression ofARID1a might decrease its combination with ER, finally affect thehypoxia-induced pathways HIF-1a/VEGF and cause the occurrence of cancer,which should be investigated in the further study.5In the endometrioid cancer, there was negative correlation of BAF250aexpression with mutated P53protein, indicating that ARID1a and P53mayinfluence each other by some mechanisms needed further investigated.