Ramez N Eskander1, Shamshad Ali, Thanh Dellinger, Heather A Lankes, Leslie M Randall, Nilsa C Ramirez, Bradley J Monk, Joan L Walker, Eric Eisenhauer, Bang H Hoang. 1. *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.
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.
RCT Entities:
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.
Authors: P W Finch; X He; M J Kelley; A Uren; R P Schaudies; N C Popescu; S Rudikoff; S A Aaronson; H E Varmus; J S Rubin Journal: Proc Natl Acad Sci U S A Date: 1997-06-24 Impact factor: 11.205
Authors: Amit M Oza; Laurie Elit; Ming-Sound Tsao; Suzanne Kamel-Reid; Jim Biagi; Diane Michele Provencher; Walter H Gotlieb; Paul J Hoskins; Prafull Ghatage; Katia S Tonkin; Helen J Mackay; John Mazurka; Joana Sederias; Percy Ivy; Janet E Dancey; Elizabeth A Eisenhauer Journal: J Clin Oncol Date: 2011-07-25 Impact factor: 44.544
Authors: Carmen J Marsit; Margaret R Karagas; Angeline Andrew; Mei Liu; Hadi Danaee; Alan R Schned; Heather H Nelson; Karl T Kelsey Journal: Cancer Res Date: 2005-08-15 Impact factor: 12.701
Authors: K Kawasaki; M Watanabe; M Sakaguchi; Y Ogasawara; K Ochiai; Y Nasu; H Doihara; Y Kashiwakura; N-h Huh; H Kumon; H Date Journal: Cancer Gene Ther Date: 2008-07-25 Impact factor: 5.987
Authors: H G Pálmer; J M González-Sancho; J Espada; M T Berciano; I Puig; J Baulida; M Quintanilla; A Cano; A G de Herreros; M Lafarga; A Muñoz Journal: J Cell Biol Date: 2001-07-23 Impact factor: 10.539
Authors: Lauren Krill; Wei Deng; Ramez Eskander; David Mutch; Susan Zweizig; Bang Hoang; Olga Ioffe; Leslie Randall; Heather Lankes; David S Miller; Michael Birrer Journal: Gynecol Oncol Date: 2019-12-13 Impact factor: 5.482
Authors: Pradip De; Jennifer Carlson Aske; Adam Dale; Luis Rojas Espaillat; David Starks; Nandini Dey Journal: Am J Transl Res Date: 2021-11-15 Impact factor: 4.060