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

Ramez N. Eskander, Shamshad Ali, Thanh Dellinger, Heather A. Lankes, Leslie M. Randall, Nilsa C. Ramirez, Bradley J. Monk, Joan L. Walker, Eric Eisenhauer, Bang H. Hoang

Research output: Contribution to journalArticle

8 Citations (Scopus)

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/m2. 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.

Original languageEnglish (US)
Pages (from-to)125-132
Number of pages8
JournalInternational Journal of Gynecological Cancer
Volume26
Issue number1
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

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Endometrioid Carcinoma
Messenger RNA
Endometrial Neoplasms
Wnt Proteins
Recurrence
Sample Size
Reverse Transcription
Disease-Free Survival
Body Mass Index
Down-Regulation
Western Blotting
rat Sfrp4 protein
frizzled related protein-1
Polymerase Chain Reaction
Proteins

Keywords

  • Dkk3
  • SFRP1
  • SFRP4
  • Uterine cancer
  • Wnt pathway

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

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. / Eskander, Ramez N.; Ali, Shamshad; Dellinger, Thanh; Lankes, Heather A.; Randall, Leslie M.; Ramirez, Nilsa C.; Monk, Bradley J.; Walker, Joan L.; Eisenhauer, Eric; Hoang, Bang H.

In: International Journal of Gynecological Cancer, Vol. 26, No. 1, 01.01.2016, p. 125-132.

Research output: Contribution to journalArticle

Eskander, Ramez N. ; Ali, Shamshad ; Dellinger, Thanh ; Lankes, Heather A. ; Randall, Leslie M. ; Ramirez, Nilsa C. ; Monk, Bradley J. ; Walker, Joan L. ; Eisenhauer, Eric ; Hoang, Bang H. / 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. In: International Journal of Gynecological Cancer. 2016 ; Vol. 26, No. 1. pp. 125-132.
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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 m{\"u}llerian 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 m{\"u}llerian 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/m2. There was a difference in Dkk3 protein expression between normal m{\"u}llerian 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.",
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T1 - Expression Patterns of the Wnt Pathway Inhibitors Dickkopf3 and Secreted Frizzled-Related Proteins 1 and 4 in Endometrial Endometrioid Adenocarcinoma

T2 - An NRG Oncology/Gynecologic Oncology Group Study

AU - Eskander, Ramez N.

AU - Ali, Shamshad

AU - Dellinger, Thanh

AU - Lankes, Heather A.

AU - Randall, Leslie M.

AU - Ramirez, Nilsa C.

AU - Monk, Bradley J.

AU - Walker, Joan L.

AU - Eisenhauer, Eric

AU - Hoang, Bang H.

PY - 2016/1/1

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N2 - 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/m2. 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.

AB - 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/m2. 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.

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