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368 Can morphology and immune infiltration predict the HRD status in newly diagnosed high grade serous ovarian carcinoma? Lessons from the PAOLA-1/ENGOT-Ov25 Trial, a GINECO study
  1. Amel Kime1,
  2. Guillaume Bataillon2,
  3. Isabelle Treilleux3,
  4. Céline Callens4,
  5. Frédéric Selle5,
  6. Florian Heitz6,
  7. Saverio Cinieri7,
  8. Antonio González-Martin8,
  9. Gerhard Bogner9,
  10. Gabriel Lindahl10,
  11. Gabriella Parma11,
  12. Ignace Vergote12,
  13. Takashi Matsumoto13,
  14. Cyriac Blonz14,
  15. Ulrich Canzler15,
  16. Anna Maria Mosconi16,
  17. Eric Pujade-Lauraine17,
  18. Catherine Genestie18,
  19. Isabelle Ray-Coquard19 and
  20. Pierre-Alexandre Just1
  1. 1Service de pathologie, Université Paris Cité, Faculté de Médecine Paris Cité, APHP.Centre, Hôpital Cochin, Paris, France
  2. 2Département d’anatomopathologie, Institut Universitaire du Cancer de Toulouse – Oncopole, Toulouse, France
  3. 3Département de biopathologie, Centre Léon Bérard, Lyon, France
  4. 4Service de Génétique, unité de Pharmacogénomique, Institut Curie, Paris, France
  5. 5Groupe Hospitalier Diaconesses Croix Saint-Simon, Paris, France
  6. 6Kliniken Essen-Mitte, Essen, Germany
  7. 7Ospedale Senatore Antonio Perrino, Brindisi, Italy
  8. 8Cancer Center, Clinica Universidad de Navarra, Madrid, Spain
  9. 9Paracelsus Medical University, Salzburg, Austria
  10. 10University Hospital, Linköping, Sweden
  11. 11European Institute of Oncology, Milan, Italy
  12. 12University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium
  13. 13Ehime University Hospital, Ehime, Japan
  14. 14Hôpital privé du Confluent, Nantes, France
  15. 15Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
  16. 16Ospedale S. Maria della Misericordia, Perugia, Italy
  17. 17ARCAGY-GINECO, Paris, France
  18. 18Département de Biologie et Pathologie Médicales, Gustave Roussy, Villejuif, France
  19. 19Centre Léon Bérard, Université Claude Bernard, Lyon, France

Abstract

Introduction/Background A correlation between the morphology of high-grade ovarian serous carcinomas (HGOSC) and BRCA mutations has been previously reported (Soslow RA, Mod Pathol, 2012). Beyond BRCA, we studied the association between the morphology of HGOSC and the presence of homologous recombination deficiency (HRD).

Methodology 522 on 806 cases of HGOSC from the PAOLA-1 clinical phase III trial were reviewed, including 163 cases with tumor BRCA mutation (tBRCAm), 345 cases without tumor BRCA mutation (tBRCAwt) and 14 cases with inconclusive BRCA tests. Regarding HRD status, 269 cases (52%) were positive (HRD+), 198 (38%) negative (HRD-) and 55 (10%) inconclusive. Morphological analysis included (i) tumor architecture (more than 25% of solid, endometrioid and transitional patterns defined a SET architecture), (ii) tumor-infiltrating intraepithelial lymphocytes (ieTILs), (iii) tumor stromal lymphocytes (sTILs), (iv) tumor necrosis, and (v) mitotic activity.

Results SET architecture (51% vs 40%, p=0.02), high number of ieTILs (16% vs. 8%, p=0.007) and more than 10% of sTILs (27% vs 18%, p=0.02) were associated with tBRCAm compared to tBRCAwt tumors, mostly with tBRCA1m tumors. These criteria were also associated with HRD status, regardless of the tumoral BRCA mutation status: 54% vs 33% (p<0.000001) for SET architecture, 14% vs 6% (p=0.008) for high number of ieTILs and 27% vs 15% (p=0.003) for more than 10% of sTILs, for HRD+ and HRD- tumors respectively. The combination of these three criteria showed high specificity (0.99 (95%CI, 0.97 – 0.99)) but low sensitivity (0.07 (95%CI, 0.04 – 0.10)) to predict HRD+ tumors. Tumor necrosis and mitotic count were not associated with BRCA or HRD statuses.

Conclusion If the morphology of HGOSC correlates with HRD status and tBRCA status, it cannot substitute for molecular analysis as validated GIS score in daily practice.

Disclosures See COI forms.

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