Study On The Expression And Significance Of Vav3 And P-Akt In Endometrial Carcinoma

Objective:Endometrial carcinoma is the most common gynecologic malignancy.In recent years,the incidence of endometrial carcinoma exsits an upward trend.Endometrial cancer has commonly been classified into two types.Type I is commonly estrogen related and typeⅡis non-estrogen related.Estrogen and its receptor play an important role in the development of typeⅠ.As one of the members of nuclear receptors superfamily,estrogen receptor(ER) has genetic and non-genetic effects.Nowadays, many ER coregulators such as SRC,PELP/MNAR,NFAT3 and so on have been investigated.Many studies indicated the ER coregulators could activate or repress ER by the signal pathways crosstalk and play important roles in the carcinogenesis and development of endometrial cancer.Vav3 is a member of the Dbl oncogen family that function as a guanine nucleotide exchange factor(GEF) and activator of Rho family small GTPases.To date,studies demonstrated that Vav3 is associated with a variety of signal molecules,including PI3K,Grb2,MAPK,and works as a adapter molecule.In 2006,the study on breast carcinoma found that Vav3 was overexpressed in human breast cancer,the overexpression of Vav3 promoted breast cancer cell growth and enhanced ER signal axis.The effects of Vav3 in cell growth and ER activity were mediated by activation of the PI3K/Akt pathway.The overexpression of Vav3 may play important roles in human breast cancer development and progression.Our previous study demonstrated the overexpression and activation of PI3K/Akt signal pathway in endometrial cancer tissues and cells.As an important signal pathway of ER,PI3K/Akt play a role in endometrial cancer.The purpose of this study was to determine the expression and potential roles of Vav3 in human endometrial cancer,discuss the correlation of Vav3 with the clinicopatholigical factors of endometrial cancer and the signal pathway of estrogen receptor.Methods:18 normal controls(NE),11 atypical hyperplasia(AHE) and 117 endometrial carcinoma cases(EC) were from General Hospital of Tianjin Medical University.The clinical cases were collected.The expressions of Vav3 and p-Akt were determined by immunohistochemistry in NE,AHE and EC.SPSS15.0 software was employed to analyze all datas.Statistical evaluation was performed using Chi-Square test,Fisher's exact test,Spearrnan's test.P＜0.05 was considered as statistical significance.Results:1.In comparison with normal endometrium,the expression of Vav3 was increased significantly in endometrial cancer and atypical hyperplasia endometrium.While there was no difference in expression of Vav3 in endometrial carcinoma and hyperplasia endometrium.The expression of Vav3 in typeⅠendometrial cancer was similar with which in typeⅡ.In typeⅠendometrial cancer,the overexpression of Vav3 was associated with high FIGO stage,high grade,deep myometrial invasion,but not associated with pelvic lymphonode metastasis and menopause;the correlation between the expression of Vav3 and ER was significant.2.In comparison with normal endometrium,the expression of p-Akt was increased significantly in endometrial cancer and atypical hyperplasia endometrium.While there was no difference in the expression of p-Akt in endometrial carcinoma and hyperplasia endometrium.In typeⅠendometrial cancer,the overexpression of p-Akt was associated with high FIGO stage,high grade,deep myometrial invasion and pelvic lymphonode metastasis,but not associated with menopause;the correlation between the expression of p-Akt and ER was significant.3.The correlation of the expressions of Vav3 and p-Akt was significant in endometrial cancer of typeⅠ.Conclusion:This study proved that the expression of Vav3 and p-Akt gradually increased from normal endometrium to endometrial carcinoma.Vav3 may play an important role in the development and progression of endometrial carcinoma,and Vav3 may crosstalk with ER signal axis by activating PI3K/Akt pathway.All need further research.