Biomarkers in Samples From Patients With Endometrial Cancer

Summary

Participation Requirements

Description

PRIMARY OBJECTIVES: I. 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) II. Determine the relationship between FGFR2 mutation and clinicopathologic variabl...

PRIMARY OBJECTIVES: I. 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) II. 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) III. 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) IV. 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) V. Confirm epigenetic biomarkers (differential methylation of CpG island loci) associated with recurrent and disease progression in endometrioid endometrial cancer from GOG-0210. (Project 2) VI. 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) VII. 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) VIII. Estimate the prevalence of HNPCC-related and other forms of inherited endometrial cancer in GOG-0210. (Project 3) IX. Define the relationship between defective DNA mismatch repair and clinical and epidemiological factors in GOG-0210. (Project 3) X. Determine the clinicopathologic significance of mismatch-repair defects including associations with disease-free and overall survival in GOG-0210. (Project 3) XI. 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) XII. 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 XIII. Determine the clinicopathologic significance of ERK substrate expression in primary endometrial cancers from WUSM and GOG-0210. (Project 4) XIV. 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) XV. 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.

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