Assessment of PARP protein expression in epithelial ovarian cancer by ELISA pharmacodynamic assay and immunohistochemistry

被引：14

作者：

Veskimae, K. ^{[1
]}

Staff, S. ^{[1
,2
]}

Gronholm, A. ^{[3
]}

Pesu, M. ^{[3
,4
]}

Laaksonen, M. ^{[5
]}

Nykter, M. ^{[5
]}

Isola, J. ^{[2
]}

Maenpaa, J. ^{[1
,6
]}

机构：

[1] Tampere Univ Hosp, Dept Gynecol & Obstet, POB 2000, Tampere 33521, Finland

[2] Univ Tampere, Inst Biomed Technol, Canc Biol Lab, BioMediTech, Tampere, Finland

[3] Univ Tampere, Inst Biosci & Med Technol, Immunoregulat, BioMediTech, Tampere, Finland

[4] Tampere Univ Hosp, Dept Dermatol, Tampere, Finland

[5] Univ Tampere, Inst Biosci & Med Technol, Tampere, Finland

[6] Univ Tampere, Sch Med, Tampere, Finland

来源：

TUMOR BIOLOGY | 2016年 / 37卷 / 09期

基金：

芬兰科学院;

关键词：

PARP; Epithelial ovarian cancer; BRCA; Platinum sensitivity; IHC; DIPHOSPHATE-RIBOSE) POLYMERASE EXPRESSION; OLAPARIB MAINTENANCE THERAPY; EX-VIVO ASSAY; HOMOLOGOUS RECOMBINATION; POLY(ADP-RIBOSE) POLYMERASE; DNA-REPAIR; NEOADJUVANT CHEMOTHERAPY; BREAST-CANCER; RIBOSE POLYMERASE; BRCA2; MUTATIONS;

D O I：

10.1007/s13277-016-5062-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：11991 / 11999

页数：9

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