Variable Expression of the Disialoganglioside GD2 in Breast Cancer Molecular Subtypes

  • Cancers (Basel). 2021 Nov 8;13(21):5577. doi: 10.3390/cancers13215577.
Ramona Erber  1 ,  Sareetha Kailayangiri  2 ,  Hanna Huebner  3 ,  Matthias Ruebner  3 ,  Arndt Hartmann  1 ,  Lothar Häberle  3  4 ,  Julia Meyer  3  4 ,  Simon Völkl  5 ,  Andreas Mackensen  5 ,  Laura Landgraf  1 ,  Carol I Geppert  1 ,  Rüdiger Schulz-Wendtland  6 ,  Matthias W Beckmann  3 ,  Peter A Fasching  3  7 ,  Nicole Farwick  2 ,  Claudia Rossig  2 ,  Paul Gass  3
Affiliations
  • 1. Institute of Pathology, Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg (FAU), Comprehensive Cancer Center Erlangen-EMN, 91054 Erlangen, Germany.
  • 2. Department of Pediatric Hematology and Oncology, Münster University Hospital, 48149 Münster, Germany.
  • 3. Department of Gynecology and Obstetrics, Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg (FAU), Comprehensive Cancer Center Erlangen-EMN, 91054 Erlangen, Germany.
  • 4. Biostatistics Unit, Department of Gynecology and Obstetrics, Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg (FAU), 91054 Erlangen, Germany.
  • 5. Department of Internal Medicine 5, Hematology/Oncology, Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg (FAU), Comprehensive Cancer Center Erlangen-EMN, 91054 Erlangen, Germany.
  • 6. Institute of Diagnostic Radiology, Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg (FAU), Comprehensive Cancer Center Erlangen-EMN, 91054 Erlangen, Germany.
  • 7. Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
PMID: 34771738 DOI: 10.3390/cancers13215577
Abstract

The disialoganglioside GD2 is a tumor-associated antigen that may allow for the application of targeted immunotherapies (anti-GD2 antibodies, GD2 CAR T cells) in patients with neuroblastoma and Other solid tumors. We retrospectively investigated GD2 expression in a breast Cancer cohort, using immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays (TMAs), and its impact on survival. GD2 expression on IHC (n = 568) and IF (n = 503) was investigated in relation to subtypes and patient outcome. Overall, 50.2% of the 568 IHC-assessed samples and 69.8% of the 503 IF-assessed samples were GD2-positive. The highest proportion of GD2-positive tumors was observed in luminal tumors. Significantly fewer GD2-positive cases were detected in triple-negative breast Cancer (TNBC) compared with Other subtypes. The proportion of GD2-expressing tumors were significantly lower in HER2-positive breast Cancer in comparison with luminal tumors on IF staining (but not IHC). GD2 expression of IHC or IF was not significantly associated with disease-free or overall survival, in either the overall cohort or in individual subtypes. However, GD2 expression can be seen in more than 50% of breast Cancer cases, with the highest frequency in hormone receptor-positive tumors. With this high expression frequency, patients with GD2-positive advanced breast Cancer of all subtypes may benefit from GD2-targeting immunotherapies, which are currently subject to clinical testing.

Keywords
GD2; breast cancer; disialoganglioside; immunofluorescence; immunohistochemistry; prognosis.
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