Length of ischemic time is critical for accurate determination of homologous recombination capacity by immunostaining in FFPE tumor samples
Karagöz, E.; Pikkusaari, S.; Tumiati, M.; Virtanen, A.; Salko, M.; Härkönen, A.; Kanerva, A.; Koskela, H.; Tapper, J.; Koivisto-Korander, R.; Joutsiniemi, T.; Haltia, U.-M.; Lassus, H.; Färkkilä, A.; Hynninen, J.; Hietanen, S.; Kauppi, L.
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Homologous recombination-deficient (HRD) high-grade serous ovarian cancers (HGSC) are more sensitive to PARP inhibitors compared to their homologous recombination-proficient counterparts. To match the right drug with the right patient the HRD status must be accurately determined. Functional HRD assays, which assess HRD status by quantifying RAD51, a key homologous recombination (HR) protein, are a promising approach for identifying HRD cases. However, these tests are yet to be optimized for pre-analytical variables, specifically HGSC tissue sampling protocols, which can impact RAD51 signal measurement. In this study, we systematically analyzed the impact of ischemic time on formalin-fixed paraffin-embedded HGSC specimens. We demonstrate that the maximum length of ischemic time compatible with accurate HRD calls is 2 hours post-excision. Our findings highlight the importance of properly monitoring and recording sample handling processes, particularly in HGSC, and warrant caution when using archival tumor material where this information is unavailable. Non-optimal pre-analytical factors like ischemic time can cause false HRD calls, thus leading to incorrect patient stratification, which may result in the initiation of treatments with potential side effects without a therapeutic benefit.
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