The Study On The Relationship Of Nuclear Receptor Coactivators AIB1 And ERα And Their Expression In Endometrial Carcinoma

OBJECTIVE To study the expression of nuclear receptor coactivators AIBl (amplified in breast cancer 1) and estrogen receptor alpha (ERa) in endometrial carcinoma and the relationship with the clinical-pathological features. And to analyze the relationship between AIBl and ERa.METHODS Using semi-quantitive reverse transcription-polymerase chain reaction (RT-PCR), we examined the expression of AIB1 and ERa mRNA. Using immunohistochemistry, we examined the expression of their protein in 51 cases of endometrial carcinomas and 47 cases of hyperplasia endometriums as well as 18 cases of normal endometriums.RESULTS 1. The expression of AIB1 mRNA (1) AIBl mRNA were detected in endometrial carcinoma, hyperplasia endometriums and normal endometriums tissues, the expression rate and average quantity of AIBlmRNA were detected in significantly greater proportion endometrial carcinomas ( 94.12% , 0.1922±0.0548 ) than in hyperplasia endometria (80.85%, 0.1353±0.0159) and endometrial tissue (61.11%, 0.1502±0.0637) , the difference has absolute significance (P<0.01) . (2) Among hyperplasia endometriums groups, the expression rate and average quantity of AIBlmRNA were detected in greater proportion atypical hyperplasia endometria (84.62%, 0.2453±0.0172) than in compex hyperplasia endometria (66.67%, 0.1227±0.0212) and simple hyperplasia endometria (42.11%, 0.1070±0.0265), the difference among above has significance (X~2=6.1329, F=4.2128, P<0.01). (3) Between normal endometriums group, the expression rate of AIB1 mRNA between hyperplasia stage and secretion stage has no significant difference (X~2=0.0117, P>0.05) .The average quantity of AIBlmRNA were detected in greater proportion secretion stage than in hyperplasia stage, the difference among above has significance(t'=2.3624, P<0.05 ). (4) Among endometrial carcinoma group, The expression of AIB1 mRNA was irrelevant to surgical-pathological stage , lymph node metastatis , pathological subtype, patients age and pathological grade (P>0.05, respectively);but related to myometrial infiltrition depth (P< 0.05) . the positive rate and the expression of average quantity of AIB1 were higher in myometrial infiltrition depth ≥1/2 than that in myometrial infiltrition depth< 1/2 .2. The expression of ERa mRNA (1) The expression rate and average quantity of ERa mRNA were detected in significantly lower proportion endometrial carcinomas than in hyperplasia endometria and endometrial tissue.The expressions difference of ERa mRNA inthree groups above demonstrated significant difference (PO.Ol) . (2) Among hyperplasia endometriums group , the expression of average quantity of ERa mRNA in atypical hyperplasia was significantly lower than in simple hyperplasia and complex hyperplasia tissues;(3 ) Between normal endometriums group, the expression of ERa between hyperplasia stage and secretion stage has no significant difference. (4) Among endometrial carcinoma group, lower ERa mRNA expression significantly correlated with pathological grade (P <0.01);The average quantity of ERa mRNA and expression rate of ERa protein were higher in Endometrioid Adenocarcinoma than other histological subtypes (P <0.05);but it has no association with clinical—surgical stage (P >0.05 )> lymph node metastasis (P >0.05)> moymetrial depth (P >0.05) and age (P>0.05).3. The expression of AIB 1 protein (1) AIB1 protein were detected in endometrial carcinoma> hyperplasia endometriums and normal endometriums tissues. The expressions rate of AIB1 protein in three groups above demonstrated significant difference(P<0.01). The expression density of AIB 1 protein detected in greater proportion endometrial carcinomas than in hyperplasia endometria and endometrial tissue,the difference has significance(P<0.05). (2) Among hyperplasia endometriums groups , the expression rate and density of AIB 1 protein were detected in greater proportion atypical hyperplasia endometria than in compex hyperplasia endometria and simple hyperplasia endometria,the difference among above has significance (PO.05) . (3) Among normal endometriums group, the expression rate and density of AIB1 protein between hyperplasia stage and secretion stage has no significant difference (P>0.05). (4) Among endometrial carcinoma group, The expression of AIB1 protein was irrelevant to surgical-pathological stage , lymph node metastatis , pathological subtype, patients age and pathological grade (P>0.05, respectively);but related to myometrial infiltrition depth (P< 0.05) . the positive expression rate and density of AIB 1 were higher in myometrial infiltrition depth ^1/2 than in myometrial infiltrition depth < 1/2 of endometrial carcinomas.4. The expression of ERa protein (1) The expressions of ERa protein in three groups above demonstrated significant difference (P<0.05). (2) Among hyperplasia endometriums group, the expression density of ERa protein in atypical hyperplasia was significantly lower than in simple hyperplasia and complex hyperplasia tissues (PO.05) . (3) Among normal endometriums group, the expression of ERa protein in hyperplasia stage was higher than in secretion stage, the difference between above has significance (PO.05) . (4) Among endometrial carcinoma group , higher ERa protein expression significantly correlated with pathological grade (P<0.01) and histological subtypeCP<0.05);but it has no association with clinical—surgical stage (jP>0.05)> lymph node metastasis (P >0.05), moymetrial depths>0.05) and age(P>0.05 ).5. The relationship between the expression of AIB1 and ERa The over expression of AIB1 mRNA and protein in endometrial carcinomas was related to the positivity of ERa. The average quantity of AIB1 mRNA and expression rate and density of AIB1 protein in endometrial carcinomars tissues with ERa protein coexpression was higher than those without ERa protein coexpression, and the difference between above has signifience ( P<0.05 ) .During the whole development of endometrial carcinomas,the relative expressions analysis between AIB1 and ERa showed negative correlations (P <0.05).CONCLUSION 1. The expression levels of AIB1 mRNA and protein in endometrial carcinomas was significantly higher than that in hyperplasia endometriums and normal endometriums , and AIB1 gene is overexpressed in endeometrial carcinomas.Overexpressed AIB1 which enhance the transcriptional activity and stability of ERa by medating ligand dependent or independent transcription was found in the early or precarcinoma terms of the endometrial neoplasms. This suggest that the abnormal overexpression of AIB1 was closed related to the development of endometrial carcinoma, and AIB 1 may be one of the factors promoting the development of endometrial carcinoma, and one of the indicators of worse clinical prognosis endometrial carcinomas.2. The expression levels of ERa mRNA and protein in endometrial carcinomas was significantly lower than that in hyperplasia endometriums and normal endometriums. Lower ERa expression significantly correlated with pathological grade from Gl to G3 .Decreased level of ERa maybe predicts high chance of worse clinical prognosis of endometrial carcinoma.3. The overexpression of AIB1 was correlated to the positivity of ERa. The average quantity of AIB 1 mRNA and expression rate and density of AIB 1 protein in emdometrial carcinomas tissues with ERa protein coexpression was higher than those without ERa protein coexpression. During the development of endometrial carcinomas , the relative expressions between AIB1 mRNA and ERa mRNA showed negative correlations. Overexpression of AIB1 maybe one of the causes of endocrine therapy resistant of endometrial neoplasms ,and the overexpression of AIB1 maybe the indicator of worse clinical prognosis endometrial carcinomas.Postgraduate students: Cui-xiu Wang (Gynecology) Directed by Prof. Yan-kui Wang...