A1 Refereed original research article in a scientific journal

Functional Homologous Recombination Assay on FFPE Specimens of Advanced High-Grade Serous Ovarian Cancer Predicts Clinical Outcomes




AuthorsPikkusaari Sanna, Tumiati Manuela, Virtanen Anni, Oikkonen Jaana, Li Yilin, Perez-Villatoro Fernando, Muranen Taru, Salko Matilda, Huhtinen Kaisa, Kanerva Anna, Koskela Heidi, Tapper Johanna, Koivisto-Korander Riitta, Joutsiniemi Titta, Haltia Ulla-Maija, Lassus Heini, Hautaniemi Sampsa, Färkkilä Anniina, Hynninen Johanna, Hietanen Sakari, Carpen Olli, Kauppi Liisa

PublisherAMER ASSOC CANCER RESEARCH

Publication year2023

JournalClinical Cancer Research

Journal name in sourceCLINICAL CANCER RESEARCH

Journal acronymCLIN CANCER RES

Volume29

Issue16

First page 3110

Last page3123

Number of pages14

ISSN1078-0432

eISSN1557-3265

DOIhttps://doi.org/10.1158/1078-0432.CCR-22-3156(external)

Web address https://aacrjournals.org/clincancerres/article/29/16/3110/728241/Functional-Homologous-Recombination-Assay-on-FFPE(external)

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/180871988(external)


Abstract

Purpose:
Deficiency in homologous recombination (HR) repair of DNA damage is characteristic of many high-grade serous ovarian cancers (HGSC). It is imperative to identify patients with homologous recombination–deficient (HRD) tumors as they are most likely to benefit from platinum-based chemotherapy and PARP inhibitors (PARPi). Existing methods measure historical, not necessarily current HRD and/or require high tumor cell content, which is not achievable for many patients. We set out to develop a clinically feasible assay for identifying functionally HRD tumors that can predict clinical outcomes.

Experimental Design:
We quantified RAD51, a key HR protein, in immunostained formalin-fixed, paraffin-embedded (FFPE) tumor samples obtained from chemotherapy-naïve and neoadjuvant chemotherapy (NACT)-treated HGSC patients. We defined cutoffs for functional HRD separately for these sample types, classified the patients accordingly as HRD or HR-proficient, and analyzed correlations with clinical outcomes. From the same specimens, genomics-based HRD estimates (HR gene mutations, genomic signatures, and genomic scars) were also determined, and compared with functional HR (fHR) status.

Results:
fHR status significantly predicted several clinical outcomes, including progression-free survival (PFS) and overall survival (OS), when determined from chemo-naïve (PFS, P < 0.0001; OS, P < 0.0001) as well as NACT-treated (PFS, P < 0.0001; OS, P = 0.0033) tumor specimens. The fHR test also identified as HRD those PARPi-at-recurrence–treated patients with longer OS (P = 0.0188).

Conclusions:
We developed an fHR assay performed on routine FFPE specimens, obtained from either chemo-naïve or NACT-treated HGSC patients, that can significantly predict real-world platinum-based chemotherapy and PARPi response.


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Last updated on 2024-26-11 at 17:48