Assessment of PARP protein expression in epithelial ovarian cancer by ELISA pharmacodynamic assay and immunohistochemistry
Assessment of PARP protein expression in epithelial ovarian cancer by ELISA pharmacodynamic assay and immunohistochemistry
复制标题
通过 ELISA 药效测定和免疫组织化学评估上皮性卵巢癌中 PARP 蛋白的表达
作者：
K. Veskimäe;S. Staff;A. Grönholm;M. Pesu;M. Laaksonen;M. Nykter;J. Isola;J. Mäenpää
靶向参与碱基切除修复（BER）的聚（ADP-核糖）聚合酶1（PARP-1）已被证明是同源重组（HR）缺陷的上皮性卵巢癌（EOC）的临床有效治疗策略。本研究的目的是通过免疫组织化学（IHC）评价新鲜EOC肿瘤组织中PAR（聚（ADP-核糖））浓度作为存档样本中PARP活性和PARP蛋白表达的替代标志物。前瞻性研究队列包括57份新鲜肿瘤样本，这些样本来自接受EOC初次（n = 38）或间隔减瘤手术（n = 19）的患者，以及平行存档的石蜡包埋肿瘤样本。通过酶化学发光测定法评估新鲜冷冻肿瘤组织中的PARP活性，并通过IHC评估石蜡包埋肿瘤组织中的PARP蛋白表达。PARP酶活性和PARP染色（通过IHC）之间未检测到相关性（p = 0.82）。在整个研究队列（p = 0.022）和高级别亚组（p = 0.017）中，高PARP活性与铂敏感性相关。高PARP活性也与无进展生存期（PFS）改善相关（32 vs 14个月，对数秩p = 0.009）。然而，PARP免疫染色模式不能预测患者的生存率。总之，我们提出了一个新的发现，即高PARP活性与EOC的铂敏感性和PFS改善相关。PARP IHC与药效学测定之间无相关性，PARP IHC与临床病理学特征和患者生存期的相关性较差。药效学试验而非IHC似乎更好地反映了具有生物学意义的PARP。
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.
BRCA1和BRCA2突变之间的关联以及侵入性上皮卵巢癌女性的生存。
影响因子：
120.7
作者：
Bolton, Kelly L.;Chenevix-Trench, Georgia;Goh, Cindy;Sadetzki, Siegal;Ramus, Susan J.;Karlan, Beth Y.;Lambrechts, Diether;Despierre, Evelyn;Barrowdale, Daniel;McGuffog, Lesley;Healey, Sue;Easton, Douglas F.;Sinilnikova, Olga;Benitez, Javier;Garcia, Maria J.;Neuhausen, Susan;Gail, Mitchell H.;Hartge, Patricia;Peock, Susan;Frost, Debra;Evans, Gareth;Eeles, Rosalind;Godwin, Andrew K.;Daly, Mary B.;Kwong, Ava;Ma, Edmond S. K.;Lazaro, Conxi;Blanco, Ignacio;Montagna, Marco;D'Andrea, Emma;Nicoletto, Maria Ornella;Johnatty, Sharon E.;Krueger, Susanne;Jensen, Allan;Hogdall, Estrid;Goode, Ellen L.;Fridley, Brooke L.;Loud, Jennifer T.;Greene, Mark H.;Mai, Phuong L.;Chetrit, Angela;Lubin, Flora;Hirsh-Yechezkel, Galit;Glendon, Gord;Andrulis, Irene L.;Toland, Amanda E.;Senter, Leigha;Gore, Martin E.;Gourley, Charlie;Michie, Caroline O.;Song, Honglin;Tyrer, Jonathan;Whittemore, Alice S.;McGuire, Valerie;Sieh, Weiva;Kristoffersson, Ulf;Olsson, Hakan;Borg, Ake;Levine, Douglas A.;Steele, Linda;Beattie, Mary S.;Chan, Salina;Nussbaum, Robert L.;Moysich, Kirsten B.;Gross, Jenny;Cass, Ilana;Walsh, Christine;Li, Andrew J.;Leuchter, Ronald;Gordon, Ora;Garcia-Closas, Montserrat;Gayther, Simon A.;Chanock, Stephen J.;Antoniou, Antonis C.;Pharoah, Paul D. P.
通讯作者：
Pharoah, Paul D. P.
影响因子：
3.8
作者：
Metzger, Michael J.;Stoddard, Barry L.;Monnat, Raymond J., Jr.
通讯作者：
Monnat, Raymond J., Jr.