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

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Názov: Can Morphology and Immune Infiltration Predict the Homologous Recombination Deficiency Status in Newly Diagnosed High-Grade Serous Ovarian Carcinoma?
Autori: Kime, Amel, Bataillon, Guillaume, Treilleux, Isabelle, Callens, Céline, Selle, Frédéric, Heitz, Florian, Cinieri, Saverio, González-Martin, Antonio, Schauer, Christian, Lindahl, Gabriel, Parma, Gabriella, Vergote, Ignace, Matsumoto, Takashi, Blonz, Cyriac, Canzler, Ulrich, Mosconi, Anna Maria, Guerra Alía, Eva María, Pujade-Lauraine, Eric, Genestie, Catherine, Ray-Coquard, Isabelle, Just, Pierre-Alexandre
Zdroj: Archives of pathology & laboratory medicine.
Informácie o vydavateľovi: College of American Pathologists, 2025.
Rok vydania: 2025
Predmety: Adult, BEVACIZUMAB, BIOMARKERS, Research & Experimental Medicine, Lymphocytes, Tumor-Infiltrating, MUTATION-STATUS, Pathology, Humans, CANCER PATIENTS, Homologous Recombination, Aged, Ovarian Neoplasms, BRCA2 Protein, Science & Technology, BRCA1 Protein, OLAPARIB, 3202 Clinical sciences, 1103 Clinical Sciences, Middle Aged, BRCA1, TUMORS, Cystadenocarcinoma, Serous, Medical Laboratory Technology, MAINTENANCE, Medicine, Research & Experimental, CELLS, Mutation, PATTERNS, Female, Neoplasm Grading, Life Sciences & Biomedicine
Popis: 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.
Druh dokumentu: Article
Jazyk: English
ISSN: 1543-2165
DOI: 10.5858/arpa.2024-0081-oa
Prístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/39648143
Prístupové číslo: edsair.pmid.dedup....a43f9fe67be0fecd7b0a5e4b1ffa7bd1
Databáza: OpenAIRE
Popis
Abstrakt: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.
ISSN:15432165
DOI:10.5858/arpa.2024-0081-oa