Jennifer Taylor Veneris1, Kathleen M Darcy2, Paulette Mhawech-Fauceglia3, Chunqiao Tian2, Ernst Lengyel4, Ricardo R Lastra5, Tanja Pejovic6, Suzanne D Conzen7, Gini F Fleming8. 1. Department of Medicine, Section of Hematology-Oncology, The University of Chicago, Chicago, IL, United States. Electronic address: jveneris@medicine.bsd.uchicago.edu. 2. Women's Health Integrated Research Center, Inova Health System, Annandale, VA, United States. 3. Department of Pathology, University of Southern California, Los Angeles, CA, United States. 4. Department of Obstetrics and Gynecology, Section of Gynecologic Oncology, The University of Chicago, Chicago, IL, United States; The University of Chicago Comprehensive Cancer Center, Chicago, IL, United States. 5. Department of Pathology, The University of Chicago, Chicago, IL, United States. 6. Department of Obstetrics and Gynecology, Section of Gynecologic Oncology, Oregon Health & Science University, Portland, OR, United States. 7. Department of Medicine, Section of Hematology-Oncology, The University of Chicago, Chicago, IL, United States; Ben May Department for Cancer Biology, The University of Chicago, Chicago, IL, United States; The University of Chicago Comprehensive Cancer Center, Chicago, IL, United States. 8. Department of Medicine, Section of Hematology-Oncology, The University of Chicago, Chicago, IL, United States; The University of Chicago Comprehensive Cancer Center, Chicago, IL, United States. Electronic address: gfleming@medicine.bsd.uchicago.edu.
Abstract
OBJECTIVE: To investigate the association of tumor glucocorticoid receptor (GR) expression and patient outcome in ovarian cancer. METHODS: GR expression was evaluated by immunohistochemistry using tissue microarrays of specimens from 481 patients with ovarian cancer and 4 patients with benign conditions. Low GR expression was defined as an intensity of 0 or 1+ and high GR as 2+ or 3+ in >1% of tumor cells. Analyses were performed to evaluate the relationship of GR expression with clinical characteristics, progression-free survival (PFS) and overall survival (OS). RESULTS: GR protein was highly expressed in 133 of 341 (39.0%) tumors from patients who underwent upfront cytoreduction surgery followed by adjuvant chemotherapy. High GR expression was more common in serous tumors (p<0.001), high grade tumors (p<0.001), and advanced stage tumors (p=0.037). Median PFS was significantly decreased in cases with high GR (20.4months) compared to those with low GR (36.0months, HR=1.66, 95% CI 1.29-2.14, p<0.001). GR remained an independent prognostic factor for PFS in multivariate analysis. OS was not associated with GR status. CONCLUSIONS: These data suggest that high GR expression correlates with poor prognosis and support the hypothesis that modulating GR activity in combination with chemotherapy may improve outcomes.
OBJECTIVE: To investigate the association of tumorglucocorticoid receptor (GR) expression and patient outcome in ovarian cancer. METHODS:GR expression was evaluated by immunohistochemistry using tissue microarrays of specimens from 481 patients with ovarian cancer and 4 patients with benign conditions. Low GR expression was defined as an intensity of 0 or 1+ and high GR as 2+ or 3+ in >1% of tumor cells. Analyses were performed to evaluate the relationship of GR expression with clinical characteristics, progression-free survival (PFS) and overall survival (OS). RESULTS:GR protein was highly expressed in 133 of 341 (39.0%) tumors from patients who underwent upfront cytoreduction surgery followed by adjuvant chemotherapy. High GR expression was more common in serous tumors (p<0.001), high grade tumors (p<0.001), and advanced stage tumors (p=0.037). Median PFS was significantly decreased in cases with high GR (20.4months) compared to those with low GR (36.0months, HR=1.66, 95% CI 1.29-2.14, p<0.001). GR remained an independent prognostic factor for PFS in multivariate analysis. OS was not associated with GR status. CONCLUSIONS: These data suggest that high GR expression correlates with poor prognosis and support the hypothesis that modulating GR activity in combination with chemotherapy may improve outcomes.
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