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High poly(adenosine diphosphate-ribose) polymerase expression and poor survival in advanced-stage serous ovarian
Jason C Barnett1, Sarah M Bean, John M Nakayama
1From 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.
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.
