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.
机构信息
Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Department of Pathology, Soonchunhyang University, Seoul, Korea.
出版信息
J Gynecol Oncol. 2023 Jul;34(4):e45. doi: 10.3802/jgo.2023.34.e45. Epub 2023 Feb 3.
OBJECTIVE
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).
METHODS
We evaluated the immunohistochemical expression of RAD51/geminin/γH2AX in ovarian HGSC before and after NAC.
RESULTS
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) (p0.032). In post-NAC tumors (n=50), the RAD51-high group (36.0%, 18/50) showed worse PFS (p0.013) and tended to present worse overall survival (p0.067) 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 (p0.046 and p0.019, 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 (p0.031).
CONCLUSION
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.
目的
RAD51 检测是一种新开发的同源重组缺陷（HRD）功能检测方法，反映实时 HRD 状态。我们旨在确定 RAD51 免疫组化表达在前、后新辅助化疗（NAC）卵巢高级别浆液性癌（HGSC）标本中的适用性和预测价值。
方法
我们评估了卵巢 HGSC 患者在 NAC 前、后 RAD51/geminin/γH2AX 的免疫组化表达。
结果
在 NAC 前肿瘤（n=51）中，74.5%（39/51）的肿瘤细胞至少有 25%的γH2AX 阳性，提示内源性 DNA 损伤。RAD51 高组（41.0%，39/51）的无进展生存期（PFS）明显较 RAD51 低组（51.3%，20/51）差（p=0.032）。在 NAC 后肿瘤（n=50）中，RAD51 高组（36.0%，18/50）的 PFS 更差（p=0.013），且总生存期更差的趋势（p=0.067），与 RAD51 低组（64.0%，32/50）相比。RAD51 高组比 RAD51 低组在 6 个月和 12 个月时更有可能进展（p=0.046 和 p=0.019）。在有匹配 NAC 前、后 RAD51 结果的 34 例患者中，34%（15/34）的 NAC 前 RAD51 结果在 NAC 后组织中发生改变，且 RAD51 高至高组的 PFS 最差，而低至低组的 PFS 最好（p=0.031）。
结论
RAD51 高表达与 HGSC 的 PFS 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，在很大一部分未经治疗的 HGSC 样本中可以评估 RAD51 状态。由于 RAD51 状态动态变化，对 RAD51 状态的连续随访可能反映 HGSC 的生物学行为。
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