RAD51/geminin/γH2AX immunohistochemical expression predicts platinum-based chemotherapy response in ovarian high-grade serous carcinomaopen access
- Authors
- Kim, Kyeongmin; Kim, Se Hoon; Lee, Jung-Yun; Kim, Yoo-Na; Lee, Seung-Tae; Park, Eunhyang
- Issue Date
- Jul-2023
- Publisher
- KOREAN SOC GYNECOLOGY ONCOLOGY & COLPOSCOPY
- Keywords
- Ovarian Cancer; RAD51 recombinase; Homologous Recombination; Neoadjuvant Chemotherapy; Immunohistochemistry
- Citation
- JOURNAL OF GYNECOLOGIC ONCOLOGY, v.34, no.4
- Journal Title
- JOURNAL OF GYNECOLOGIC ONCOLOGY
- Volume
- 34
- Number
- 4
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/26474
- DOI
- 10.3802/jgo.2023.34.e45
- ISSN
- 2005-0380
2005-0399
- Abstract
- 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/& gamma;H2AX in ovarian HGSC before and after NAC. Results: In pre-NAC tumors (n=51), 74.5% (39/51) showed at least 25% of & gamma;H2AX-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).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-naive HGSC samples. As RAD51 status dynamically changes, sequential follow-up of RAD51 status might reflect the biological behavior of HGSCs.
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