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PD-L1 Expression in Premalignant and Malignant Trophoblasts From Gestational Trophoblastic Diseases Is Ubiquitous and Independent of Clinical Outcomes
  1. Pierre-Adrien Bolze, MD*,,,
  2. Sophie Patrier, MD,§,
  3. Jérôme Massardier, MD,
  4. Touria Hajri, MSc,,
  5. Fatima Abbas, MD,,
  6. Anne Marie Schott, MD, PhD,,
  7. Fabienne Allias, MD,#,
  8. Mojgan Devouassoux-Shisheboran, MD, PhD,#,
  9. Gilles Freyer, MD, PhD,**,
  10. François Golfier, MD, PhD*, and
  11. Benoît You, MD, PhD,**,††
  1. *Department of Gynecological Surgery and Oncology, Obstetrics, and
  2. French Center for Trophoblastic Diseases, University Hospitals of Lyon; and
  3. Joint Unit Hospices Civils de Lyon-bioMerieux, University Hospital Lyon Sud, Pierre Bénite;
  4. §Department of Pathology, University Hospital of Rouen, Rouen;
  5. University Hospital Femme Mere Enfant, Department of Prenatal Diagnosis; and
  6. Pôle Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Bron; and
  7. #Department of Pathology, University Hospital La Croix Rousse;
  8. **Department of Medical Oncology, HCL Cancer Institute, University Hospitals of Lyon; and
  9. ††Lyon 1 University, Lyon, France.
  1. Address correspondence and reprint requests to Pierre-Adrien Bolze, MD, French Center for Trophoblastic Diseases, University Hospitals of Lyon, Centre Hospitalier Lyon Sud, 165, Chemin du Grand Revoyet, Bâtiment 3B, 2ème étage, 69495 Pierre Bénite, France. E-mail: pierre-adrien.bolze@chu-lyon.fr.

Abstract

Objective Recently reported expression of programmed cell death 1 ligand 1 (PD-L1) in gestational trophoblastic diseases (GTDs) suggests that the immune tolerance of pregnancy might be hijacked during neoplastic process. We assessed PD-L1 protein expression in premalignant and malignant GTD lesions and analyzed associations with disease severity and chemotherapy outcomes.

Methods We included 83 GTD whole-tissue sections from 76 patients in different treatment settings. PD-L1 protein expression was assessed with immunohistochemistry in each trophoblast subtype with the Allred total score (ATS), which combines intensity and proportion expression on a 0- to 8-point scale. Peritumoral immune infiltrate was scored on hematoxylin-eosin-safran–stained slides.

Results PD-L1 expression was ubiquitous and strong in all GTD trophoblast subtypes. For invasive moles, ATS scores were maximal at 8 in 100%, 100%, and 75% of syncytiotrophoblast, villous cytotrophoblast, and extravillous cytotrophoblast specimens, respectively. For choriocarcinomas, ATS was 8 in 80% of specimens. Immune infiltrates were moderate to severe in 61%, 100%, and 100% of peritumoral zones of choriocarcinoma, epithelioid trophoblastic tumor, and invasive moles, respectively. Because of the homogeneous pathological findings, no significant differences in PD-L1 expression profiles or peritumoral immune infiltrates were found regarding FIGO (International Federation of Gynecology Obstetrics) prognostic score, fatal outcome, or chemosensitivity.

Conclusions We confirm that PD-L1 is constitutively expressed in all GTD premalignant and malignant trophoblast subtypes, independently from FIGO score, chemoresistance, or fatal outcomes, thereby suggesting a crucial role for PD-L1 in the development and tolerance of GTD. Assessment of anti–PD-L1 drug in GTD patients has been activated.

  • Choriocarcinoma
  • Gestational trophoblastic disease
  • Hydatidiform mole
  • Immunotherapy
  • PD-L1
  • Trophoblastic neoplasia

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Footnotes

  • P.A.B. was supported by fellowships from the Nuovo-Soldati Foundation for Cancer Research, from the Collège National des Gynécologues et Obstétriciens Français (CNGOF) and the Région Rhône Alpes (Explo’RA doc). The French Center for Trophoblastic Diseases was funded by the French Ligue Nationale contre le Cancer and the Institut National du Cancer.

  • The authors declare no conflicts of interest.

  • The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation; and the decision to submit the manuscript for publication.

  • Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.ijgc.net).

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