Biomarkers in Samples From Patients With Endometrial Cancer

• Rate and spectrum of mutations in fibroblast growth factor receptor 2 (FGFR2) (Project 1) [ Designated as safety issue: No ]
  
• Relationship between FGFR2 mutation and clinicopathologic (CP) variables (Project 1) [ Designated as safety issue: No ]
  
• Identification of the cognate FGF ligands and receptors expressed in normal endometrium and endometrial cancers and their expression on multiple tissue microarrays (Project 1) [ Designated as safety issue: No ]
  
• Epigenetic biomarkers associated with recurrence and disease progression (Project 2) [ Designated as safety issue: No ]
  
• Development of 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 (Project 3) [ Designated as safety issue: No ]
  
• Relationship between defective DNA mismatch repair and clinical and epidemiological factors (Project 3) [ Designated as safety issue: No ]
  
• CP significance of mismatch-repair defects (Project 3) [ Designated as safety issue: No ]
  
• Expression and relationships of five candidate ERK1/2 substrates, and substrate phosphorylation, and ERK signaling pathway activation (Project 4) [ Designated as safety issue: No ]
  
• CP significance of ERK substrate expression (Project 4) [ Designated as safety issue: No ]
  

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.