Can Morphology and Immune Infiltration Predict the Homologous Recombination Deficiency Status in Newly Diagnosed High-Grade Serous Ovarian Carcinoma?

Autor:	Kime A; From the Department of Pathology, Université Paris Cité, Faculté de Médecine Paris Cité, APHP, Centre, Hôpital Cochin, Paris, France (Kime, Just).; the Centre Hospitalier Universitaire Amiens-Picardie Site Nord, Amiens, France (Kime)., Bataillon G; the Department of Pathology, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France (Bataillon)., Treilleux I; the Department of Biopathology, Centre Léon Bérard, Lyon, France (Treilleux)., Callens C; the Department of Genetics, Pharmacogenomic Unity, Institut Curie, et Paris Sciences Lettres Université, Paris, France (Callens)., Selle F; the Department of Medical Oncology, Groupe Hospitalier Diaconesses Croix Saint-Simon, Paris, France (Selle)., Heitz F; Department of Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany (Heitz)., Cinieri S; the Department of Medical Oncology, Ospedale Senatore Antonio Perrino, Brindisi, Italy (Cinieri)., González-Martin A; the Department of Medical Oncology, Clinica Universidad de Navarra, Madrid, Spain (González-Martin)., Schauer C; the Department of Obstetrics and Gynecology, Konventhospital Barmherzige Brueder, Graz, Austria (Schauer)., Lindahl G; Departement of Oncology, University Hospital, Linköping, Sweden (Lindahl)., Parma G; the Department of Gynecological Oncology, European Institute of Oncology, Milan, Italy (Parma)., Vergote I; the Department of Gynecological Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium (Vergote)., Matsumoto T; the Department of Gynecology and Obstetrics, Ehime University Hospital, Ehime, Japan (Matsumoto)., Blonz C; the Department of Medical Oncology, Hôpital privé du Confluent, Nantes, France (Blonz)., Canzler U; the Department of Gynecology, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany (Canzler)., Mosconi AM; the Department of Medical Oncology, Ospedale S. Maria della Misericordia, Perugia, Italy (Mosconi)., Guerra Alía EM; the Department of Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid (Guerra Alia)., Pujade-Lauraine E; the Department of Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid (Guerra Alia)., Genestie C; the Department of Medical Biology and Pathology, Gustave Roussy, Villejuif, France (Genestie)., Ray-Coquard I; the Department of Medical Oncology, Centre Léon Bérard, Université Claude Bernard, Lyon, France (Ray-Coquard)., Just PA; From the Department of Pathology, Université Paris Cité, Faculté de Médecine Paris Cité, APHP, Centre, Hôpital Cochin, Paris, France (Kime, Just).; the Department of Pathology, AP-HM, Hôpital de la Timone, Marseille, France (Just).
Jazyk:	angličtina
Zdroj:	Archives of pathology & laboratory medicine [Arch Pathol Lab Med] 2024 Dec 09. Date of Electronic Publication: 2024 Dec 09.
DOI:	10.5858/arpa.2024-0081-OA
Abstrakt:	Context.—: A correlation between the morphology of ovarian high-grade serous carcinomas (HGSOCs) and BRCA mutations has been previously reported. Objective.—: To investigate, beyond BRCA, the association between the morphology of HGSOC and the presence of homologous recombination deficiency (HRD). Design.—: 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). Results.—: 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). Conclusions.—: The morphology of HGSOC correlates with HRD status and BRCA status but cannot substitute for molecular analysis in daily practice. (© 2024 College of American Pathologists.)
Databáze:	MEDLINE
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