RAD51/geminin/γH2AX免疫组化表达预测卵巢高级别浆液性癌对铂类化疗的反应。
RAD51/geminin/γH2AX immunohistochemical expression predicts platinum-based chemotherapy response in ovarian high-grade serous carcinoma.
发表日期:2023 Feb 03
作者:
Kyeongmin Kim, Se Hoon Kim, Jung-Yun Lee, Yoo-Na Kim, Seung-Tae Lee, Eunhyang Park
来源:
Journal of Gynecologic Oncology
摘要:
RAD51检测是一种新近开发的功能性检测方法,用于检测同源重组缺陷(HRD)的实时状态。我们的目的是评价RAD51在卵巢高级别浆液性癌(HGSC)新辅助化疗(NAC)前后样本中免疫组化表达的适用性和预测价值。我们评价了NAC前后卵巢HGSC中RAD51 / geminin / γH2AX的免疫组化表达。在NAC前的肿瘤(n = 51)中,74.5%(39/51)显示出至少25%的γH2AX阳性肿瘤细胞,表明存在内源性DNA损伤。RAD51高表达组(41.0%,16/39)的无进展生存期(PFS)明显较低,与RAD51低表达组(51.3%,20/39)相比(p = 0.032)。在NAC后的肿瘤(n = 50)中,RAD51高表达组(36.0%,18/50)PFS较差(p = 0.013),总生存期趋向较差(p = 0.067),与RAD51低表达组(64.0%,32/50)相比。在6个月和12个月时,RAD51高表达病例更有可能出现进展(p = 0.046和p = 0.019,分别)。在匹配NAC前后的34例患者中,44%(15/34)的NAC前RAD51结果在NAC后组织中发生了变化,RAD51高到高组的PFS最差,而低到低组的PFS最好(p = 0.031)。在HGSC中,高RAD51表达与PFS较差显著相关,NAC后RAD51状态比NAC前RAD51状态具有更高的相关性。此外,RAD51状态可以在相当一部分未接受治疗的HGSC样本中进行评估。由于RAD51状态动态改变,对RAD51状态进行序列随访可能反映HGSC的生物行为。© 2023年。亚洲妇产肿瘤学会,韩国妇产肿瘤学会和日本妇产肿瘤学会。
The RAD51 assay is a recently developed functional assay for homologous recombination deficiency (HRD) that reflects real-time HRD status. We aimed to identify the applicability and predictive value of RAD51 immunohistochemical expression in pre- and post-neoadjuvant chemotherapy (NAC) samples of ovarian high-grade serous carcinoma (HGSC).We evaluated the immunohistochemical expression of RAD51/geminin/γH2AX in ovarian HGSC before and after NAC.In pre-NAC tumors (n=51), 74.5% (39/51) showed at least 25% of γH2AX-positive tumor cells, suggesting endogenous DNA damage. The RAD51-high group (41.0%, 16/39) showed significantly worse progression-free survival (PFS) compared to the RAD51-low group (51.3%, 20/39) (p=0.032). In post-NAC tumors (n=50), the RAD51-high group (36.0%, 18/50) showed worse PFS (p=0.013) and tended to present worse overall survival (p=0.067) compared to the RAD51-low group (64.0%, 32/50). RAD51-high cases were more likely to progress than RAD51-low cases at both 6 months and 12 months (p=0.046 and p=0.019, respectively). Of 34 patients with matched pre- and post-NAC RAD51 results, 44% (15/34) of pre-NAC RAD51 results were changed in the post-NAC tissue, and the RAD51 high-to-high group showed the worst PFS, while the low-to-low group showed the best PFS (p=0.031).High RAD51 expression was significantly associated with worse PFS in HGSC, and post-NAC RAD51 status showed higher association than pre-NAC RAD51 status. Moreover, RAD51 status can be evaluated in a significant proportion of treatment-naïve HGSC samples. As RAD51 status dynamically changes, sequential follow-up of RAD51 status might reflect the biological behavior of HGSCs.© 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.