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Expression Patterns of the Wnt Pathway Inhibitors Dickkopf3 and Secreted Frizzled-Related Proteins 1 and 4 in Endometrial Endometrioid Adenocarcinoma: An NRG Oncology/Gynecologic Oncology Group Study. | LitMetric
*Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California, Irvine, Medical Center, Orange, CA; †Gynecologic Oncology Group, Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY; ‡Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, City of Hope Comprehensive Cancer Center, Duarte, CA; §The Research Institute at Nationwide Children's Hospital, Columbus, OH; ∥Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Arizona Cancer Center, Creighton University School of Medicine, St Joseph's Hospital and Medical Center, Phoenix, AZ; ¶Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Oklahoma, Oklahoma City, OK; #Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, OH; and **Department of Orthopedic Surgery, University of California, Irvine, Orange, CA.
Published: January 2016
AI Article Synopsis
Article Abstract
Objective: The aim of the study was to determine the differential expression patterns of the wingless-type (Wnt) pathway inhibitors Dkk3 (Dickkopf 3), SFRP1 (secreted frizzled-related protein 1), and SFRP4 in normal müllerian tissue and endometrial endometrioid adenocarcinoma specimens.
Methods: Messenger RNA (mRNA) and protein levels of the Wnt pathway inhibitors Dkk3, SFRP1, and SFRP4 were evaluated by real-time reverse transcription-polymerase chain reaction and Western blot analysis. A total of 87 human tissue specimens were obtained from 60 women who participated in Gynecologic Oncology Group protocol 210. Twenty-seven normal müllerian tissues, 32 early-stage, and 28 advanced-stage endometrial endometrioid cancer specimens were analyzed.
Results: Median age for this cohort was 60 years, with median body mass index of 32 kg/m. There was a difference in Dkk3 protein expression between normal müllerian tissues and primary endometrial endometrioid adenocarcinoma samples (P = 0.05). There was down-regulation of Dkk3, SFRP1, and SFRP4 mRNA expression in patients with high-grade disease (P = 0.08, 0.06, and 0.05, respectfully). Furthermore, a decrease in SFRP1 and SFPR4 mRNA expression was noted in patients with a diagnosis of locoregional and distant disease recurrence. Lastly, a trend toward decreased progression-free survival in patients with low Dkk3, SFRP1, and SFRP4 mRNA expression levels was noted.
Conclusions: Wnt pathway inhibitor (Dkk3, sFRP1, and/or sFRP4) expression was down-regulated in patients with high-grade disease and was associated with locoregional and distant disease recurrence. Despite sample size (power) limitations, these results support previous preclinical studies and may suggest a therapeutic role for Wnt signaling in endometrial cancer.
