title: Assessment of PARP protein expression in epithelial ovarian cancer by ELISA pharmacodynamic assay and immunohistochemistry.
abstract: Targeting Poly (ADP-ribose) polymerase 1 (PARP-1) involved in base excision repair (BER) has been shown to be a clinically effective treatment strategy in epithelial ovarian cancer (EOC) defective in homologous recombination (HR). The aim of this study was to evaluate fresh EOC tumor tissue in regard to PAR (Poly (ADP-ribose)) concentration as a surrogate marker for PARP activity and PARP protein expression in archival samples by immunohistochemistry (IHC). The prospective study cohort consisted of 57 fresh tumor samples derived from patients undergoing primary (n = 38) or interval debulking surgery (n = 19) for EOC and parallel archival paraffin-embedded tumor samples. PARP activity in fresh frozen tumor tissue was assessed by an enzymatic chemiluminescence assay and PARP protein expression in paraffin-embedded tumor tissue by IHC. No correlation was detected between PARP enzyme activity and PARP staining by IHC (p = 0.82). High PARP activity was associated with platinum sensitivity both in the entire study cohort (p = 0.022) and in the high-grade subgroup (p = 0.017). High PARP activity was also associated with improved progression-free survival (PFS) (32 vs 14 months, log-rank p = 0.009). However, PARP immunostaining pattern was not predictive of patient survival. In conclusion, we present a novel finding of high PARP activity associated with platinum sensitivity and improved PFS in EOC. There was no association between PARP IHC and pharmacodynamic assay, and the correlation of PARP IHC with clinico-pathological characteristics and patient survival was poor. Pharmacodynamic assay rather than IHC seems to reflect better biologically significant PARP.
authors.affiliation: Department of Gynecology and Obstetrics, Tampere University Hospital, PO Box 2000, 33521, Tampere, Finland. kristina.veskimae@fimnet.fi.
authors.forename: K
authors.initials: K
authors.lastname: Veskimäe
authors.affiliation: Department of Gynecology and Obstetrics, Tampere University Hospital, PO Box 2000, 33521, Tampere, Finland.|Laboratory of Cancer Biology, Institute of Biomedical Technology, BioMediTech, University of Tampere, Tampere, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Staff
authors.affiliation: Immunoregulation, Institute of Biosciences and Medical Technology, BioMediTech, University of Tampere, Tampere, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Grönholm
authors.affiliation: Immunoregulation, Institute of Biosciences and Medical Technology, BioMediTech, University of Tampere, Tampere, Finland.|Department of Dermatology, Tampere University Hospital, Tampere, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Pesu
authors.affiliation: Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Laaksonen
authors.affiliation: Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Nykter
authors.affiliation: Laboratory of Cancer Biology, Institute of Biomedical Technology, BioMediTech, University of Tampere, Tampere, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Isola
authors.affiliation: Department of Gynecology and Obstetrics, Tampere University Hospital, PO Box 2000, 33521, Tampere, Finland.|School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Mäenpää
mesh_terms: D000368:Aged; D000077216:Carcinoma, Ovarian Epithelial; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology* / Q000401:mortality / Q000628:therapy; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000628:therapy; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000032:analysis* / Q000037:antagonists & inhibitors; D011446:Prospective Studies
chemical_list: D000071137:Poly (ADP-Ribose) Polymerase-1
keywords: BRCA; Epithelial ovarian cancer; IHC; PARP; Platinum sensitivity