Jason C Barnett1, Sarah M Bean, John M Nakayama, Eiji Kondoh, Susan K Murphy, Andrew Berchuck. 1. From the Department of Obstetrics and Gynecology/Division of Gynecologic Oncology and Department of Pathology, Duke University Medical Center, Durham, North Carolina; Department of Gynecology and Obstetrics, Kyoto University, Kyoto, Japan; and Duke Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina.
Abstract
OBJECTIVE: To estimate the range of poly(adenosine diphosphate [ADP]-ribose) polymerase expression in serous ovarian cancers and to determine whether expression is associated with response to therapy and outcome. METHODS: Immunostaining for poly(ADP-ribose) polymerase was performed in 186 paraffin-embedded, serous ovarian cancers. Nuclear poly(ADP-ribose) polymerase expression was quantified using a scoring system that assesses both staining intensity and percentage of cells staining. Kaplan-Meier analysis was performed to evaluate the relationship between poly(ADP-ribose) polymerase expression and overall survival. RESULTS: High poly(ADP-ribose) polymerase expression was present in 54% of serous cancers but was not associated with stage or grade. There was no difference in the rate of complete clinical response to primary chemotherapy between cases with low poly(ADP-ribose) polymerase expression (70%) compared with those with high poly(ADP-ribose) polymerase expression (71%). However, high poly(ADP-ribose) polymerase expression was associated with significantly worse median overall survival (36 compared with 43 months, P=.04, hazard ratio 0.71). CONCLUSION: Expression of poly(ADP-ribose) polymerase in ovarian cancers is heterogeneous, and high expression in serous ovarian cancers is associated with worse overall survival. These data suggest that evaluation of poly(ADP-ribose) polymerase expression in the primary cancer could potentially allow selective use of poly(ADP-ribose) polymerase inhibitors in patients most likely to respond. LEVEL OF EVIDENCE: III.
OBJECTIVE: To estimate the range of poly(adenosine diphosphate [ADP]-ribose) polymerase expression in serous ovarian cancers and to determine whether expression is associated with response to therapy and outcome. METHODS: Immunostaining for poly(ADP-ribose) polymerase was performed in 186 paraffin-embedded, serous ovarian cancers. Nuclear poly(ADP-ribose) polymerase expression was quantified using a scoring system that assesses both staining intensity and percentage of cells staining. Kaplan-Meier analysis was performed to evaluate the relationship between poly(ADP-ribose) polymerase expression and overall survival. RESULTS: High poly(ADP-ribose) polymerase expression was present in 54% of serous cancers but was not associated with stage or grade. There was no difference in the rate of complete clinical response to primary chemotherapy between cases with low poly(ADP-ribose) polymerase expression (70%) compared with those with high poly(ADP-ribose) polymerase expression (71%). However, high poly(ADP-ribose) polymerase expression was associated with significantly worse median overall survival (36 compared with 43 months, P=.04, hazard ratio 0.71). CONCLUSION: Expression of poly(ADP-ribose) polymerase in ovarian cancers is heterogeneous, and high expression in serous ovarian cancers is associated with worse overall survival. These data suggest that evaluation of poly(ADP-ribose) polymerase expression in the primary cancer could potentially allow selective use of poly(ADP-ribose) polymerase inhibitors in patients most likely to respond. LEVEL OF EVIDENCE: III.
Authors: Jung-Min Lee; John L Hays; Christina M Annunziata; Anne M Noonan; Lori Minasian; Jo Anne Zujewski; Minshu Yu; Nicolas Gordon; Jiuping Ji; Tristan M Sissung; William D Figg; Nilofer Azad; Bradford J Wood; James Doroshow; Elise C Kohn Journal: J Natl Cancer Inst Date: 2014-05-19 Impact factor: 13.506
Authors: Erika J Lampert; John L Hays; Elise C Kohn; Christina M Annunziata; Lori Minasian; Minshu Yu; Nicolas Gordon; Tristan M Sissung; Victoria L Chiou; William D Figg; Nicole Houston; Jung-Min Lee Journal: Oncotarget Date: 2019-04-23