Reduced Expression of DKK3 Is Associated With Adverse Clinical Outcomes of Uterine Cervical Squamous Cell Carcinoma
- Authors
- Ryu, Seok-Woo; Kim, Jae Hyung; Kim, Mi Kyung; Lee, Youn-Jeong; Park, Jun-Soo; Park, Hyoung-Moo; Kim, Dong-Ho; Lee, Sang-Hoon; Lee, Eun-Ju
- Issue Date
- Jan-2013
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Keywords
- Cervical cancer; DKK3; Beta-catenin
- Citation
- INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, v.23, no.1, pp 134 - 140
- Pages
- 7
- Journal Title
- INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
- Volume
- 23
- Number
- 1
- Start Page
- 134
- End Page
- 140
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/14992
- DOI
- 10.1097/IGC.0b013e3182754feb
- ISSN
- 1048-891X
1525-1438
- 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. Materials and 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: DICK3 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. Conclusion: 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.
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