Trial Information

Specialized Program of Research Excellence (SPORE) in Endometrial Cancer

OBJECTIVES:

- Assess the frequency and spectrum of mutations in fibroblast growth factor receptor 2
(FGFR2) in low-, intermediate-, and/or high-risk endometrioid endometrial cancer from
GOG-0210. (Project 1)

- Determine the relationship between FGFR2 mutation and clinicopathologic variables
including disease-free and overall survival in low-, intermediate-, and/or high-risk
endometrial cancer from GOG-0210. (Project 1)

- Identify the cognate FGF ligands and receptors expressed in normal endometrium and
endometrial cancers, and examine their expression on multiple tissue microarrays for
GOG-0210 to determine their association with clinical outcome. (Project 1)

- Identify epigenetic biomarkers (differential methylation of CpG island loci) associated
with recurrence and disease progression in endometrioid endometrial cancer from
Washington University School of Medicine (WUSM). (Project 2)

- Confirm epigenetic biomarkers (differential methylation of CpG island loci) associated
with recurrent and disease progression in endometrioid endometrial cancer from
GOG-0210. (Project 2)

- Define the performance (sensitivity and specificity) of epigenetic biomarkers
associated with recurrence and disease progression in endometrioid endometrial cancer
from an independent cohort of cases from GOG-0210. (Project 2)

- Develop a molecular screening regimen to compliment family history risk assessment to
identify carriers of Hereditary Non-Polyposis Colorectal Cancer (HNPCC)-related and
other forms of inherited endometrial cancer from GOG-0210 that was not ascertained by
family history. (Project 3)

- Estimate the prevalence of HNPCC-related and other forms of inherited endometrial
cancer in GOG-0210. (Project 3)

- Define the relationship between defective DNA mismatch repair and clinical and
epidemiological factors in GOG-0210. (Project 3)

- Determine the clinicopathologic significance of mismatch-repair defects including
associations with disease-free and overall survival in GOG-0210. (Project 3)

- Assess expression of five candidate ERK1/2 substrates in the normal endometrium,
primary endometrial cancers (from WUSM and GOG-0210) and endometrial cancer cell lines
and determine if substrate phosphorylation is ERK-dependent. (Project 4)

- Determine the relationship between ERK substrate-phosphorylation status and upstream
ERK-signaling pathway activation in primary endometrial cancers from WUSM and GOG-0210.
(Project 4)

- Determine the clinicopathologic significance of ERK substrate expression in primary
endometrial cancers from WUSM and GOG-0210. (Project 4)

- Explore GSK3/3 inhibition as a therapeutic treatment of endometrial cancer and assess
the role of inhibiting other ERK substrates in endometrial cell lines. (Project 4)

- Explore the predictive and prognostic accuracy of a panel of single nucleotide
polymorphisms alone and with informative clinical, surgical, and pathologic variables
in a cohort of Caucasian women with stage IB or IC vs IIIC endometrioid endometrial
cancer from WUSM and GOG-0210. (Project 5)

OUTLINE: This is a multicenter study.

Previously collected samples are analyzed for biomarker and other laboratory analyses.