title: Prognostic significance of annexin A2 and annexin A4 expression in patients with cervical cancer.
abstract: The annexins (ANXs) have diverse roles in tumor development and progression, however, their clinical significance in cervical cancer has not been elucidated. The present study was to investigate the clinical significance of annexin A2 (ANXA2) and annexin A4 (ANXA4) expression in cervical cancer.
  
  
  
  ANXA2 and ANXA4 immunohistochemical staining were performed on a cervical cancer tissue microarray consisting of 46 normal cervical epithelium samples and 336 cervical cancer cases and compared the data with clinicopathological variables, including the survival of cervical cancer patients.
  
  
  
  ANXA2 expression was lower in cancer tissue (p = 0.002), whereas ANXA4 staining increased significantly in cancer tissues (p < 0.001). ANXA2 expression was more prominent in squamous cell carcinoma (p < 0.001), whereas ANXA4 was more highly expressed in adeno/adenosquamous carcinoma (p < 0.001). ANXA2 overexpression was positively correlated with advanced cancer phenotypes, whereas ANXA4 expression was associated with resistance to radiation with or without chemotherapy (p = 0.029). Notably, high ANXA2 and ANXA4 expression was significantly associated with shorter disease-free survival (p = 0.004 and p = 0.033, respectively). Multivariate analysis indicated that ANXA2+ (HR = 2.72, p = 0.003) and ANXA2+/ANXA4+ (HR = 2.69, p = 0.039) are independent prognostic factors of disease-free survival in cervical cancer. Furthermore, a random survival forest model using combined ANXA2, ANXA4, and clinical variables resulted in improved predictive power (mean C-index, 0.76) compared to that of clinical-variable-only models (mean C-index, 0.70) (p = 0.006).
  
  
  
  These findings indicate that detecting ANXA2 and ANXA4 expression may aid the evaluation of cervical carcinoma prognosis.
authors.affiliation: Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, MSC 1500, Bethesda, MD, 20892, USA.|Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea.
authors.forename: Chel Hun
authors.initials: CH
authors.lastname: Choi
authors.affiliation: Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, MSC 1500, Bethesda, MD, 20892, USA.
authors.forename: Joon-Yong
authors.initials: JY
authors.lastname: Chung
authors.affiliation: Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD, 20892, USA.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Chung
authors.affiliation: Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, MSC 1500, Bethesda, MD, 20892, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Sears
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea.
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea. ds123.bae@samsung.com.
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Bae
authors.affiliation: Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, MSC 1500, Bethesda, MD, 20892, USA. genejock@helix.nih.gov.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
mesh_terms: D000328:Adult; D017306:Annexin A2 / Q000378:metabolism*; D017314:Annexin A4 / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D018196:Carcinoma, Adenosquamous / Q000401:mortality / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D046888:Tissue Array Analysis; D002583:Uterine Cervical Neoplasms / Q000401:mortality / Q000473:pathology*
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D017314:Annexin A4; D014408:Biomarkers, Tumor
keywords: ANXA2; ANXA4; Prognosis; Survival; Uterine cervical neoplasms