title: Reduced expression of DKK3 is associated with adverse clinical outcomes of uterine cervical squamous cell carcinoma.
abstract: OBJECTIVE
  The aim of this study was to assess the expression of DKK3 protein and its target, beta-catenin, in uterine cervical squamous cell carcinoma and to determine potential clinical correlations.
  
  
  METHODS
  Six carcinoma in-situ (CIS) tissues and 88 invasive cervical cancer tissues were included in the study. Twenty-two normal cervical tissues and one gastric cancer tissue were used as controls. The expression of DKK3 and beta-catenin proteins was evaluated by immunohistochemical analysis. Clinical and pathological parameters were obtained from medical records. Survival data were estimated using Kaplan-Meier estimates and compared with a log-rank test. Multivariate analysis was performed using the Cox regression method.
  
  
  RESULTS
  DKK3 was predominantly present in the cytoplasm. Beta-catenin was observed only on the cellular membrane of both normal and cancer cells in contrast to earlier reports, in which beta-catenin was localized to the cytoplasm and nucleus of cancer cells. The expressions of beta-catenin and DKK3 were not correlated. Three of 6 CIS (50%) and 57 of 88 invasive cancer specimens (64.8%) had lower DKK3 expression than normal controls. DKK3 expression was decreased in a stage-dependent manner (P = 0.021). The patients with low expression of DKK3 were older than those with high expression of DKK3 (P < 0.01). Moreover, the patients with low DKK3 expression had a significantly lower 5-year disease-free survival rate than those with high DKK3 expression (P = 0.026). A multivariate analysis showed that International Federation of Gynecology and Obstetrics clinical stage and parametrial involvement were independent prognostic factors.
  
  
  CONCLUSIONS
  Decreased DKK3 expression was associated with advanced International Federation of Gynecology and Obstetrics clinical stages and was predictive of lower disease-free survival in patients with cervical squamous cell carcinoma. DKK3 may be implicated in cervical carcinogenesis through a beta-catenin-independent mechanism.
authors.affiliation: Department of Obstetrics and Gynecology, Chung-Ang University School of Medicine, Seoul, Korea.
authors.forename: Seok-Woo
authors.initials: SW
authors.lastname: Ryu
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Kim
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Youn-Jeong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jun-Soo
authors.initials: JS
authors.lastname: Park
authors.forename: Hyoung-Moo
authors.initials: HM
authors.lastname: Park
authors.forename: Dong-Ho
authors.initials: DH
authors.lastname: Kim
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D015536:Down-Regulation; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051176:beta Catenin