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Cerebellar degeneration-related proteins 2 and 2-like are present in ovarian cancer in patients with and without Yo antibodies

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Abstract

Background

Cerebellar degeneration-related protein 2 (CDR2) has been presumed to be the main antigen for the onconeural antibody Yo, which is strongly associated with ovarian cancer and paraneoplastic cerebellar degeneration (PCD). Recent data show that Yo antibodies also target the CDR2-like protein (CDR2L). We, therefore, examined the expression of CDR2 and CDR2L in ovarian cancer tissue from patients with and without Yo antibodies and from various other cancerous and normal human tissues.

Methods

Ovarian cancer tissue and serum samples from 16 patients were included in the study (four with anti-Yo and PCD, two with anti-Yo without PCD, five with only CDR2L antibodies, and five without onconeural antibodies). Clinical data were available for all patients. The human tissues were examined by western blot and immunohistochemistry using rabbit CDR2 and CDR2L antibodies.

Results

Ovarian cancers from all 16 patients expressed CDR2 and CDR2L proteins. Both proteins were also present in normal and cancer tissue from mammary tissue, kidney, ovary, prostate, and testis.

Conclusion

CDR2L is present in ovarian cancers from patients with and without Yo antibodies as was shown previously for CDR2. In addition, both CDR2 and CDR2L proteins are more widely expressed than previously thought, both in normal and cancerous tissues.

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Abbreviations

CDR1:

Cerebellar degeneration-related protein 1

CDR2:

Cerebellar degeneration-related protein 2

CDR2L:

Cerebellar degeneration-related protein 2-like

CDR2L1-5 :

Patients with only CDR2L antibodies detected by RIA

Control1-5 :

Control patients without antibodies

FIGO:

International Federation of Gynecology and Obstetrics

HGSC:

High-grade serous carcinoma

kDa:

Kilodalton

PCD:

Paraneoplastic cerebellar degeneration

PNS:

Paraneoplastic neurological syndrome

RIA:

Radioimmunoassay

Yo1-6 :

Patients with Yo antibodies

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Acknowledgements

The authors wish to commemorate late Helga Salvesen, MD Professor at the Department of Gynaecology and Obstetrics, Haukeland University Hospital, Norway and Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Norway, in appreciation of her great enthusiasm and knowledge. She contributed greatly to this project by including cancer samples from the Bergen Gynecologic Cancer Biobank. We also thank Miletic Hrvoje, MD PhD at the Department of Pathology, Haukeland University Hospital, Bergen and Department of Biomedicine, University of Bergen, for the reconsideration of the pathological specimens, and Manja Schubert, ScD at the Department of Neurology, Haukeland University Hospital, Bergen, for valuable advice and discussion.

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Authors and Affiliations

  1. Department of Clinical Medicine, University of Bergen, Jonas Lies veg 87, 5021, Bergen, Norway

    Margrethe Raspotnig & Christian A. Vedeler

  2. Department of Neurology, Haukeland University Hospital, Jonas Lies veg 65, 5021, Bergen, Norway

    Mette Haugen, Anette Storstein & Christian A. Vedeler

  3. Department of Pathology, The Gade Institute, Haukeland University Hospital, Jonas Lies veg 65, 5021, Bergen, Norway

    Maria Thorsteinsdottir & Ingunn Stefansson

  4. Centre for Cancer Biomarkers, Department of Clinical Science, Section for Pathology, University of Bergen, Jonas Lies veg 87, 5021, Bergen, Norway

    Ingunn Stefansson & Helga B. Salvesen

  5. Department of Gynaecology and Obstetrics, Haukeland University Hospital, Jonas Lies veg 65, 5021, Bergen, Norway

    Helga B. Salvesen

Authors
  1. Margrethe Raspotnig
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  2. Mette Haugen
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  3. Maria Thorsteinsdottir
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  4. Ingunn Stefansson
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  5. Helga B. Salvesen
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  6. Anette Storstein
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  7. Christian A. Vedeler
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Correspondence to Margrethe Raspotnig.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed involving human participants were approved by The Regional Committee for Health and Medical Research Ethics (2014/1066) and were in accordance with the Declaration of Helsinki (1964) and its later amendments or comparable ethical standards. Informed consent was obtained from living patients included in the study.

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Raspotnig, M., Haugen, M., Thorsteinsdottir, M. et al. Cerebellar degeneration-related proteins 2 and 2-like are present in ovarian cancer in patients with and without Yo antibodies. Cancer Immunol Immunother 66, 1463–1471 (2017). https://doi.org/10.1007/s00262-017-2041-8

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  • DOI: https://doi.org/10.1007/s00262-017-2041-8

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