Hjortkjær Mette, Waldstrøm Marianne, Jakobsen Anders, Kanstrup Hanne, Søgaard-Andersen Erik, Dahl Steffensen Karina
Departments of Oncology (M.H., A.J., H.K., K.D.S.) Pathology (M.W.), Vejle Hospital, Vejle Department of Gynaecology and Obstetrics (M.H., E.S.A.), Aalborg University Hospital, Aalborg Institute of Regional Health Research (M.H., M.W., A.J., K.D.S.), University of Southern Denmark, Odense Department of Gynaecology and Obstetrics (M.H.), Viborg Hospital, Viborg, Denmark.
Int J Gynecol Pathol. 2017 Mar;36(2):180-189. doi: 10.1097/PGP.0000000000000310.
BRCA1/2 mutation status in epithelial ovarian cancer (EOC) presently relies on genetic testing which is resource consuming. Immunohistochemistry is cheap, fairly reproducible, and may identify gene product alterations due to both germline and somatic mutations and other defects along the BRCA gene pathway (BRCAness phenomenon), which is important when treatment with poly (adenosine-diphosphate-ribose) polymerase (PARP) inhibitors is considered. The aim of this study was to investigate immunohistochemical detection of BRCA1 and PARP expression in EOC and their possible prognostic relevance. Tumor tissue from 170 patients with EOC was stained immunohistochemically with BRCA1 and PARP antibodies. Semiquantitative analyses were performed to determine loss of, equivocal, and retained BRCA1 and high versus low PARP protein expression. These parameters were analyzed for relation with patient and clinicopathologic characteristics and overall survival. BRCA1 expression was reduced in 21.2 % of the tumors and 36.5% showed high PARP expression. No correlation between the 2 parameters or between PARP and clinicopathologic features was found. Overall survival was significantly increased in the BRCA1-reduced and equivocal groups [median survival 2.4 y (95% CI, 1.6-6.6) and 4.9 y (95 % CI, 2.3-6.7) vs. 1.5 y (95% CI, 1.3-1.9); P=0.0002]. Multivariate analysis confirmed these findings; hazard ratio=0.53 (95% CI, 0.34-0.81; P=0.0037; loss of BRCA1 expression). In conclusion, immunohistochemical BRCA1 expression in EOC holds considerable prognostic information, whereas PARP expression did not influence the outcome. The results call for validation in prospective trials.
目前，上皮性卵巢癌（EOC）中BRCA1/2的突变状态依赖于资源消耗型的基因检测。免疫组化成本低廉、具有相当高的可重复性，并且可以识别由于种系和体细胞突变以及BRCA基因途径中的其他缺陷（BRCAness现象）导致的基因产物改变，在考虑使用聚（二磷酸腺苷-核糖）聚合酶（PARP）抑制剂进行治疗时，这一点很重要。本研究的目的是调查EOC中BRCA1和PARP表达的免疫组化检测及其可能的预后相关性。对170例EOC患者的肿瘤组织进行BRCA1和PARP抗体免疫组化染色。进行半定量分析以确定BRCA1的缺失、不明确和保留情况以及PARP蛋白的高表达与低表达。分析这些参数与患者及临床病理特征和总生存期的关系。21.2%的肿瘤中BRCA1表达降低，36.5%显示PARP高表达。未发现这两个参数之间或PARP与临床病理特征之间存在相关性。BRCA1降低组和不明确组的总生存期显著延长[中位生存期分别为2.4年（95%CI，1.6 - 6.6）和4.9年（95%CI，2.3 - 6.7），而另一组为1.5年（95%CI，1.3 - 1.9）；P = 0.0002]。多因素分析证实了这些结果；风险比 = 0.53（95%CI，0.34 - 0.81；P = 0.0037；BRCA1表达缺失）。总之，EOC中免疫组化检测BRCA1表达具有重要的预后信息，而PARP表达不影响预后。这些结果需要在前瞻性试验中进行验证。
