- Email: [email protected]
Wnt signaling in human granulosa cell tumors of the ovary
210
Abstracts / Gynecologic Oncology 145 (2017) 2–220
ovarian cancers, gynecologic generalists can consider complete surgical staging for borderline ovarian tumors when diagnosed on frozen analysis. doi:10.1016/j.ygyno.2017.03.481
455 - Poster Session Differential effects of saturated and unsaturated fatty acids on ovarian cancer growth M.H. Uddina, T.E. Buekersb, M.A. Elshaikhb, S. Girib, A.R. Munkarahb, R. Rattanb. aHenry Ford Hospital, Detroit, MI, USA, bHenry Ford Health System, Detroit, MI, USA
454 - Poster Session Wnt signaling in human granulosa cell tumors of the ovary H.D. Reyesa, B. Kilonzoa, T. Neffa, E. Devora, K.K. Lesliea, M. Samuelsona, E. Cohenb, M.J. Goodhearta. aUniversity of Iowa Hospitals and Clinics, Iowa City, IA, USA, bUniversity of Iowa, Iowa City, IA, USA Objective: Ovarian granulosa cell tumor (GCT) is a malignant type of sex-cord stromal tumor that accounts for approximately 2%–5% of all ovarian malignancies. GCTs are often identified at an early stage, but advanced disease can be quite challenging to treat. Beta-catenin (CTNNB1) and lymphoid enhancer factor-1 (LEF1) are transcriptional regulators involved in the Wnt signaling pathway that has been associated with tumor growth. Our objective is to determine whether there is an association between the Wnt signaling pathway and human ovarian GCT. Methods: Using 12 human ovarian GCT samples and 6 normal ovarian tissue controls identified through retrospective data review, snap-frozen and paraffin-embedded tissues were homogenized for RNA extraction. Expression of CTNNB1 and LEF1 was examined using quantitative RT- PCR. Gene expression data were then correlated with clinical outcomes. Results: There was a 1.8-fold increase in relative gene expression of CTNNB1 (P = 0.367) and a 24.4-fold increase in the relative expression of LEF-1 (P = 0.009) in GCTs compared to benign ovarian controls (Fig. 1). During the 8-year follow-up period between January 1990 and December 1998, 4 of the 12 patients with GCT died of the disease. When subcategorizing the patients between those who died and those who were alive during the 8-year followup, those who died had a 141.8-fold higher LEF1 expression compared to normal ovarian controls (P = 0.094), while those who were alive had 16.9-fold higher LEF1 expression (P = 0.026). Conclusion: Wnt signaling appears to be activated in human ovarian GCT with LEF1 being a potential cadidate as a therapeutic target. Continued research is needed in uncovering the role of Wnt signaling in this rare tumor type.
Objective: Free fatty acids (FFAs) acquired from the omentum have been demonstrated to promote epithelial ovarian cancer growth (EOC). Different FFAs (saturated or unsaturated) are involved in different physiological functions. The present study was designed to investigate and compare the effects of oleate, the most abundant circulating unsaturated FFA, to those of the saturated FFA palmitate in established human ovarian cancer cell lines. Method: Ovarian cancer cell lines (A2780, OVCAR5, CaOV3, and ID8) were exposed to various concentrations of either oleate (C:18:1) or palmitate (C:16) after overnight serum starvation. Proliferation and survival were measured over 72 hours by Promega proliferation assay and MTT. Apoptosis was measured by caspase 3 activity (Promega). Expression of free fatty acid receptor (FFAR) 1 and 4 was measured after exposure to oleate and palmitate by quantitative polymerase chain reaction. Results: The unsaturated FA oleate stimulated cell proliferation in a time-and dose-dependent manner (P ranges from 0.05 to 0.01 for various cells and time points) in the 4 ovarian cell lines. On the contrary, palmitate caused apoptotic cell death in all 4 ovarian cancer cell lines in a time- and dose-dependent manner (P ranges from 0.05 to 0.001 for various cells and time points). Interestingly, when all 4 cell lines were exposed to a combination of both FAs, the final effect was increased cell proliferation; in fact, oleate seemed to protect the cancer cells against the apoptotic action of palmitate in a dosedependent manner. Blocking of FFAR1 reversed the proliferative effect of oleate in ovarian cancer cells (P b 0.05–0.001). Oleate induced the pro-oncogenic signaling of AKT, while palmitate inhibited it. Conclusion: Different fatty acids have distinct effect on ovarian cancer cell proliferation and apoptosis. While the unsaturated FFA oleate promotes proliferation likely by activating Akt, the saturated FFA palmitate appears to cause apoptosis and inhibits Akt. The type of FFA and their ratios in the tumor environment may influence ovarian cancer growth and progression. This will be further investigated in vivo and patient-derived specimens. doi:10.1016/j.ygyno.2017.03.483
456 - Poster Session To screen or not to screen: Occult malignancies associated with extramammary Paget’s disease A.R. Schmitt, B.J. Long, A.L. Weaver, M. McGree, J.N. Bakkum-Gamez, J.D. Brewer, B.A. Cliby. Mayo Clinic, Rochester, MN, USA
Fig. 1.
doi:10.1016/j.ygyno.2017.03.482
Objective: To describe the rate of occult malignancies and to outline cancer screening strategies for patients with newly diagnosed extramammary Paget’s disease (EMPD). Method: Medical records of patients at a single institution seen for primary EMPD between 1992 and 2015 were reviewed. Patient, primary tumor, screening tests, and occult malignancy characteristics were abstracted. Descriptive statistics were performed. Results: Among 81 females, the mean age at presentation was 71.6 years (range 50.6–94.7), and 68 (84.0%) had at least 1 cancer screening test performed after being diagnosed with EMPD (Table 1).
Abstracts / Gynecologic Oncology 145 (2017) 2–220
ovarian cancers, gynecologic generalists can consider complete surgical staging for borderline ovarian tumors when diagnosed on frozen analysis. doi:10.1016/j.ygyno.2017.03.481
455 - Poster Session Differential effects of saturated and unsaturated fatty acids on ovarian cancer growth M.H. Uddina, T.E. Buekersb, M.A. Elshaikhb, S. Girib, A.R. Munkarahb, R. Rattanb. aHenry Ford Hospital, Detroit, MI, USA, bHenry Ford Health System, Detroit, MI, USA
454 - Poster Session Wnt signaling in human granulosa cell tumors of the ovary H.D. Reyesa, B. Kilonzoa, T. Neffa, E. Devora, K.K. Lesliea, M. Samuelsona, E. Cohenb, M.J. Goodhearta. aUniversity of Iowa Hospitals and Clinics, Iowa City, IA, USA, bUniversity of Iowa, Iowa City, IA, USA Objective: Ovarian granulosa cell tumor (GCT) is a malignant type of sex-cord stromal tumor that accounts for approximately 2%–5% of all ovarian malignancies. GCTs are often identified at an early stage, but advanced disease can be quite challenging to treat. Beta-catenin (CTNNB1) and lymphoid enhancer factor-1 (LEF1) are transcriptional regulators involved in the Wnt signaling pathway that has been associated with tumor growth. Our objective is to determine whether there is an association between the Wnt signaling pathway and human ovarian GCT. Methods: Using 12 human ovarian GCT samples and 6 normal ovarian tissue controls identified through retrospective data review, snap-frozen and paraffin-embedded tissues were homogenized for RNA extraction. Expression of CTNNB1 and LEF1 was examined using quantitative RT- PCR. Gene expression data were then correlated with clinical outcomes. Results: There was a 1.8-fold increase in relative gene expression of CTNNB1 (P = 0.367) and a 24.4-fold increase in the relative expression of LEF-1 (P = 0.009) in GCTs compared to benign ovarian controls (Fig. 1). During the 8-year follow-up period between January 1990 and December 1998, 4 of the 12 patients with GCT died of the disease. When subcategorizing the patients between those who died and those who were alive during the 8-year followup, those who died had a 141.8-fold higher LEF1 expression compared to normal ovarian controls (P = 0.094), while those who were alive had 16.9-fold higher LEF1 expression (P = 0.026). Conclusion: Wnt signaling appears to be activated in human ovarian GCT with LEF1 being a potential cadidate as a therapeutic target. Continued research is needed in uncovering the role of Wnt signaling in this rare tumor type.
Objective: Free fatty acids (FFAs) acquired from the omentum have been demonstrated to promote epithelial ovarian cancer growth (EOC). Different FFAs (saturated or unsaturated) are involved in different physiological functions. The present study was designed to investigate and compare the effects of oleate, the most abundant circulating unsaturated FFA, to those of the saturated FFA palmitate in established human ovarian cancer cell lines. Method: Ovarian cancer cell lines (A2780, OVCAR5, CaOV3, and ID8) were exposed to various concentrations of either oleate (C:18:1) or palmitate (C:16) after overnight serum starvation. Proliferation and survival were measured over 72 hours by Promega proliferation assay and MTT. Apoptosis was measured by caspase 3 activity (Promega). Expression of free fatty acid receptor (FFAR) 1 and 4 was measured after exposure to oleate and palmitate by quantitative polymerase chain reaction. Results: The unsaturated FA oleate stimulated cell proliferation in a time-and dose-dependent manner (P ranges from 0.05 to 0.01 for various cells and time points) in the 4 ovarian cell lines. On the contrary, palmitate caused apoptotic cell death in all 4 ovarian cancer cell lines in a time- and dose-dependent manner (P ranges from 0.05 to 0.001 for various cells and time points). Interestingly, when all 4 cell lines were exposed to a combination of both FAs, the final effect was increased cell proliferation; in fact, oleate seemed to protect the cancer cells against the apoptotic action of palmitate in a dosedependent manner. Blocking of FFAR1 reversed the proliferative effect of oleate in ovarian cancer cells (P b 0.05–0.001). Oleate induced the pro-oncogenic signaling of AKT, while palmitate inhibited it. Conclusion: Different fatty acids have distinct effect on ovarian cancer cell proliferation and apoptosis. While the unsaturated FFA oleate promotes proliferation likely by activating Akt, the saturated FFA palmitate appears to cause apoptosis and inhibits Akt. The type of FFA and their ratios in the tumor environment may influence ovarian cancer growth and progression. This will be further investigated in vivo and patient-derived specimens. doi:10.1016/j.ygyno.2017.03.483
456 - Poster Session To screen or not to screen: Occult malignancies associated with extramammary Paget’s disease A.R. Schmitt, B.J. Long, A.L. Weaver, M. McGree, J.N. Bakkum-Gamez, J.D. Brewer, B.A. Cliby. Mayo Clinic, Rochester, MN, USA
Fig. 1.
doi:10.1016/j.ygyno.2017.03.482
Objective: To describe the rate of occult malignancies and to outline cancer screening strategies for patients with newly diagnosed extramammary Paget’s disease (EMPD). Method: Medical records of patients at a single institution seen for primary EMPD between 1992 and 2015 were reviewed. Patient, primary tumor, screening tests, and occult malignancy characteristics were abstracted. Descriptive statistics were performed. Results: Among 81 females, the mean age at presentation was 71.6 years (range 50.6–94.7), and 68 (84.0%) had at least 1 cancer screening test performed after being diagnosed with EMPD (Table 1).