ORIGINAL ARTICLE Assessment of PARP protein expression in epithelial ovarian cancer by ELISA pharmacodynamic assay and immunohistochemistry K. Veskimäe 1 & S. Staff 1,2 & A. Grönholm 3 & M. Pesu 3,4 & M. Laaksonen 5 & M. Nykter 5 & J. Isola 2 & J. Mäenpää 1,6 Received: 16 January 2016 /Accepted: 1 May 2016 # International Society of Oncology and BioMarkers (ISOBM) 2016 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 sur- rogate 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 fro- zen tumor tissue was assessed by an enzymatic chemilumines- cence 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 immuno- staining pattern was not predictive of patient survival. In con- clusion, 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 phar- macodynamic assay, and the correlation of PARP IHC with clinico-pathological characteristics and patient survival was poor. Pharmacodynamic assay rather than IHC seems to re- flect better biologically significant PARP. Keywords PARP . Epithelial ovarian cancer . BRCA . Platinum sensitivity . IHC Introduction Epithelial ovarian cancer (EOC) is a heterogeneous disease with distinct epidemiological, phenotypical, and molecular subtypes including high-grade serous carcinoma (HGSC), low-grade serous, mucinous, endometrioid, and clear cell car- cinoma [1]. Genetically complex and unstable HGSC is the most prevalent histotype and responsible for the highest mor- tality associated with EOC [1]. Cytoreductive surgery followed by platinum-taxane based combination chemotherapy is the cornerstone of the treatment of EOC [2]. Although initial response rates to chemotherapy are high, majority of patients will relapse, leading ultimately to the development of chemoresistance [3]. Therefore, unraveling the molecular mechanisms leading to platinum re- sistance constitutes a true challenge in current EOC research. There is emerging evidence that sufficiently functional DNA repair and intact homologous recombination are major determi- nants of platinum resistance [4, 5]. The detailed analysis of EOC * K. Veskimäe kristina.veskimae@fimnet.fi 1 Department of Gynecology and Obstetrics, Tampere University Hospital, PO Box 2000, 33521 Tampere, Finland 2 Laboratory of Cancer Biology, Institute of Biomedical Technology, BioMediTech, University of Tampere, Tampere, Finland 3 Immunoregulation, Institute of Biosciences and Medical Technology, BioMediTech, University of Tampere, Tampere, Finland 4 Department of Dermatology, Tampere University Hospital, Tampere, Finland 5 Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland 6 School of Medicine, University of Tampere, Tampere, Finland Tumor Biol. DOI 10.1007/s13277-016-5062-6