Lauren Krill1, Wei Deng2, Ramez Eskander3, David Mutch4, Susan Zweizig5, Bang Hoang6, Olga Ioffe7, Leslie Randall8, Heather Lankes9, David S Miller10, Michael Birrer11. 1. Division of Gynecologic Oncology, MD Anderson Cancer Center at Cooper, Camden, NJ, United States of America. Electronic address: krill-lauren@cooperhealth.edu. 2. NRG Oncology, Clinical Trial Development Division, Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States of America. Electronic address: dengw@nrgoncology.org. 3. Department of Obstetrics, Gynecology and Reproductive Medicine, Division of Gynecologic Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA, United States of America. Electronic address: eskander@uci.edu. 4. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University; St. Louis, MO. Electronic address: mutchd@wudosis.wustl.edu. 5. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology; University of Massachusetts; Worcester, MA, United States of America. Electronic address: susan.zweizig@umassmemorial.org. 6. Department of Orthopedic Surgery, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, Bronx, NY, United States of America. Electronic address: bahoang@montefiore.org. 7. Department of Pathology, University of Maryland Medical Center; Baltimore, MD 21201, United States of America. Electronic address: oioffe@umaryland.edu. 8. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California Irvine, Orange, CA, United States of America. Electronic address: lrandall@uci.edu. 9. Biopathology Center, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States of America; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, Columbus, OH, United States of America. Electronic address: LankesH@NRGOncology.org. 10. Department of Obstetrics & Gynecology, University of Texas Southwestern Medical Center; Dallas, TX 75390-9032, United States of America. Electronic address: David.Miller@UTSouthwestern.edu. 11. Department of Medicine, Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL, United States of America. Electronic address: mbirrer@uab.edu.
Abstract
OBJECTIVES: Enhancer of zeste homolog 2 (EZH2) is a histone methyl transferase that mediates epigenetic silencing of tumor suppressor genes. It is commonly over-expressed in several solid tumors and has been shown to be a prognostic biomarker. We investigated patterns of EZH2 expression in endometrial cancer. METHODS: Evaluation of EZH2 expression was completed on both early and advanced stage endometrioid adenocarcinoma tissues and a subset of matched normal mullerian tissue samples, from participants enrolled in Gynecologic Oncology Group (GOG) protocol 210, using real time reverse transcription polymerase chain reaction (RT-PCR) and western blot (WB) analysis. Non-parametric methods were used to assess differences in mRNA and protein expression respectively with known clinical/pathologic prognostic factors. Survival analysis was performed using techniques including Cox proportional hazards (PH) model to evaluate differences in progression free survival (PFS) and overall survival (OS) based on EZH2 expression. RESULTS: Eighty-seven patient samples were analyzed that included 60 tumors and 27 matched-normal tissue specimens. EZH2 mRNA (p < .0001) and protein expression (p < .0001) in tumor specimens were significantly higher than in matched-normal tissue. In primary tumors, EZH2 protein expression was associated with lympho-vascular space invasion (LVSI, p = .044), and EZH2 mRNA expression was associated with age (p = .037). Differences in EZH2 expression between primary tumors and matched normal tissue were not associated with other known clinical and pathologic factors. However, there did appear to be a trend toward decreased progression-free survival among patients with high EZH2 expression levels. CONCLUSIONS: Our results confirm the differential expression of EZH2 in uterine cancers compared to normal tissues. However, there were no statistically significant differences in survival associated with EZH2 expression in patients with endometrial cancer. NCT #: NCT00340808.
OBJECTIVES:Enhancer of zeste homolog 2 (EZH2) is a histone methyl transferase that mediates epigenetic silencing of tumor suppressor genes. It is commonly over-expressed in several solid tumors and has been shown to be a prognostic biomarker. We investigated patterns of EZH2 expression in endometrial cancer. METHODS: Evaluation of EZH2 expression was completed on both early and advanced stage endometrioid adenocarcinoma tissues and a subset of matched normal mullerian tissue samples, from participants enrolled in Gynecologic Oncology Group (GOG) protocol 210, using real time reverse transcription polymerase chain reaction (RT-PCR) and western blot (WB) analysis. Non-parametric methods were used to assess differences in mRNA and protein expression respectively with known clinical/pathologic prognostic factors. Survival analysis was performed using techniques including Cox proportional hazards (PH) model to evaluate differences in progression free survival (PFS) and overall survival (OS) based on EZH2 expression. RESULTS: Eighty-seven patient samples were analyzed that included 60 tumors and 27 matched-normal tissue specimens. EZH2 mRNA (p < .0001) and protein expression (p < .0001) in tumor specimens were significantly higher than in matched-normal tissue. In primary tumors, EZH2 protein expression was associated with lympho-vascular space invasion (LVSI, p = .044), and EZH2 mRNA expression was associated with age (p = .037). Differences in EZH2 expression between primary tumors and matched normal tissue were not associated with other known clinical and pathologic factors. However, there did appear to be a trend toward decreased progression-free survival among patients with high EZH2 expression levels. CONCLUSIONS: Our results confirm the differential expression of EZH2 in uterine cancers compared to normal tissues. However, there were no statistically significant differences in survival associated with EZH2 expression in patients with endometrial cancer. NCT #: NCT00340808.
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