title: Expression and clinical significance of annexin A2 and human epididymis protein 4 in endometrial carcinoma.
abstract: BACKGROUND
  It is well-known that the treatment and monitoring methods are limited for advanced stage of endometrial carcinoma. Biological molecules with expression changes during tumor progression become potential therapeutic targets for advanced stage endometrial carcinoma. Annexin A2 (ANXA2) has been reported to be overexpressed in recurrent endometrial carcinoma, and the expression of human epididymis protein 4 (HE4) is upregulated in endometrial carcinoma. What's more, ANXA2 and HE4 interacted in ovarian cancer and promoted the malignant biological behavior. We speculated that their interaction may exist in endometrial carcinoma as well. We evaluated the expression and the correlation relationship of ANXA2 and HE4 in endometrial carcinoma.
  
  
  METHODS
  The expression of ANXA2 and HE4 protein in 84 endometrial carcinoma, 30 endometrial atypical hyperplasia, and 18 normal endometrial tissue samples were then measured using an immunohistochemical assay in paraffin embedded endometrial tissues. The structural relationship between ANXA2 and HE4 was explored by immunoprecipitation and double immunofluorescent staining.
  
  
  RESULTS
  ANXA2 and HE4 co-localized in both endometrial tissues and endometrial carcinoma cells. ANXA2 and HE4 were expressed in 95.2 % and 85.7 % of the the endometrial carcinoma, respectively, which were significantly higher than normal endometrium (55.6 % and 16.7 %, both p < 0.05). The expression of ANXA2 and HE4 was significantly correlated with FIGO stage, degree of differentiation, myometrial invasion, and lymph node metastasis. ANXA2 was an independent risk factor for the prognosis of endometrial carcinoma (p < 0.05, hazard ratio [HR] = 8.004). The expression of ANXA2 and HE4 was positively correlated (Spearman correlation coefficient = 0.228, p < 0.05). HE4 was an independent factor for ANXA2 in multivariate linear regression model (p < 0.05).
  
  
  CONCLUSIONS
  We revealed the co-localization of ANXA2 and HE4 in endometrial carcinoma. Expression levels of ANXA2 and HE4 were closely related to the malignant biological behavior of endometrial carcinoma, and ANXA2 was an independent risk factor for poor prognosis. The expression of ANXA2 and HE4 can affect each other.
authors.affiliation: Department of Gynaecology and Obstetrics, Shengjing Hospital affiliated to China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China. denglu90@hotmail.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Gynaecology and Obstetrics, Shengjing Hospital affiliated to China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China. 904150770@qq.com.|Tianjin Central Hospital of Gynaecology and Obstetrics, Tianjin, China. 904150770@qq.com.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Gynaecology and Obstetrics, Shengjing Hospital affiliated to China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China. lixiaojs@163.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Gynaecology and Obstetrics, Shengjing Hospital affiliated to China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China. caimingbo01@163.com.|Department of Obstetrics and Gynecology, Hospital of Zhengzhou University, Zhengzhou, Henan, China. caimingbo01@163.com.
authors.forename: Mingbo
authors.initials: M
authors.lastname: Cai
authors.affiliation: Department of Gynaecology and Obstetrics, Shengjing Hospital affiliated to China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China. 1151761600@qq.com.
authors.forename: Huimin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Gynaecology and Obstetrics, Shengjing Hospital affiliated to China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China. 458547577@qq.com.|Department of Gynecology and Obstetrics, Beijing chaoyang Hospital, Capital Medical University, Beijing, China. 458547577@qq.com.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: Department of Gynaecology and Obstetrics, Shengjing Hospital affiliated to China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China. kitefly1102@126.com.
authors.forename: Mingzi
authors.initials: M
authors.lastname: Tan
authors.affiliation: Department of Gynaecology and Obstetrics, Shengjing Hospital affiliated to China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China. liushuice@163.com.
authors.forename: Shuice
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Gynaecology and Obstetrics, Shengjing Hospital affiliated to China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China. 18940258190@163.com.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Department of Gynaecology and Obstetrics, Shengjing Hospital affiliated to China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China. linbei88@hotmail.com.
authors.forename: Bei
authors.initials: B
authors.lastname: Lin
mesh_terms: D017306:Annexin A2 / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000556:secondary; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011506:Proteins / Q000378:metabolism*; D012372:ROC Curve; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D014408:Biomarkers, Tumor; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human