A correlation between the morphology of ovarian high-grade serous carcinomas (HGSOCs) and BRCA mutations has been previously reported.
To investigate, beyond BRCA, the association between the morphology of HGSOC and the presence of homologous recombination deficiency (HRD).
We reviewed 522 of 806 cases of HGSOC from the PAOLA-1 clinical trial, including 163 cases with tumor BRCA mutation, 345 cases without tumor BRCA mutation, and 14 cases with inconclusive BRCA tests. Regarding HRD status (myChoice HRD Plus assay), 269 cases (52%) were positive (HRD+), 198 (38%) negative (HRD−), and 55 (10%) inconclusive. Morphologic analysis included tumor architecture (with more than 25% of solid, pseudoendometrioid, and transitional patterns defining a SET architecture), tumor-infiltrating intraepithelial lymphocytes (ieTILs), and tumor stromal lymphocytes (sTILs).
SET architecture (51% versus 40%, P = .02), high number of ieTILs (16% versus 8%, P = .007) and more than 10% of sTILs (27% versus 18%, P = .02) were associated with tumor BRCA mutation, mostly for tumors with a BRCA1 mutation. These criteria were also associated with HRD status: 54% versus 33% (P < .001) for SET architecture, 14% versus 6% (P = .008) for high number of ieTILs, and 27% versus 15% (P = .003) for more than 10% of sTILs. SET architecture was also significantly associated with HRD+ tumors without tumor BRCA mutation (P < .001) when compared with HRD− tumors. The combination of these 3 criteria showed high specificity (0.99; 95% CI, 0.97–0.99) but low sensitivity (0.07; 95% CI, 0.04–0.10).
The morphology of HGSOC correlates with HRD status and BRCA status but cannot substitute for molecular analysis in daily practice.
Author notes
The PAOLA-1/ENGOT-ov25 is an international clinical trial that was conducted in 11 countries with different national collaborative networks. The following authors are associated with these participating networks: GINECO, France (Kime, Just, Bataillon, Treilleux, Selle, Blonz, Genestie, Ray-Coquard); AGO, Germany/Austria (Heitz, Schauer, Canzler); MITO, Italy (Cinieri, Mosconi); MaNGO, Italy (Parma); GEICO, Spain (González-Martin, Guerra Alia); NSGO, Sweden (Lindahl); BGOG, Belgium (Vergote); and GOTIC, Japan (Matsumoto). Pujade-Lauraine is an employee of GINECO.
Heitz received financial compensation from NovoCure, PharmaMar, GSK, MSD, AstraZeneca, Roche, Tesaro Inc, Clovis, amedes, AbbVie Inc, Immunogen, Inc, and Seagen Inc. Matsumoto receives honoraria from AstraZeneca, Chugai Pharma, and MSD. The other authors have no relevant financial interest in the products or companies described in this article.
Results were presented in part at the European Society of Gynaecological Oncology (ESGO) 2024 25th European Congress on Gynaecological Oncology; March 7–10, 2024; Barcelona, Spain.
Bataillon and Treilleux contributed equally to this work