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Expression of CD3, PD-L1 and CTLA-4 in mammary and extra-mammary Paget disease

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Background

Mammary and extra-mammary Paget disease is a rare form of intra-epithelial glandular neoplasm which is characteristically recurrent and necessitates multiple excisions that have an important impact on morbidity. Local immuno-modulating treatments have been applied with promising results, but the local immune markers of Paget disease have not been studied.

Aim of the study

To investigate the local immune micro-environment of Paget disease.

Materials and methods

Sixty-four specimens from 41 patients, including cases with multiple recurrences and underlying primary neoplasm, have been studied for their expression of CD3, PD-L1 and CTLA-4.

Results

Nineteen cases were mammary; 22 were extra-mammary and involved the vulva, the anus, the inguinal region and the lower extremity. PD-L1 was not expressed by any neoplastic lesion or the associated lymphocytes. CTLA-4 expression was found in nine cases. Higher stromal CD3 expression and moderate levels of intra-epithelial CD3 expression were present in most cases. Biopsies, subsequent excision specimens and recurrences showed the same immunohistochemical profile of CD3 and PD-L1, although there were different levels of CTLA-4 in a few cases. The underlying lesions in mammary Paget disease showed the same immunohistochemical profile as the intra-epithelial neoplastic cells. The expression of the markers did not correlate with age, sex, localization or recurrence.

Conclusion

Paget disease is characterized by an intense lymphocytic response, devoid of the immune-suppressive impact of the PD-L1 pathway, but with occasional CTLA-4 expression.

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Abbreviations

CIN:

Cervical intra-epithelial neoplasia

DCIS:

Ductal carcinoma in situ

EMPD:

Extra-mammary Paget disease

FDA:

Food and Drug Administration

MPD:

Mammary Paget disease

PD:

Paget disease

RANK/RANKL:

Receptor activator of nuclear factor kappa B ligand

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Acknowledgements

The authors would like to thank Mr Philippe Cosmo from the Tumorothèque/Centre de Ressources Biologiques de CHU Saint-Etienne (BRIF no. BB-0033-00041) for his assistance.

Funding

No relevant funding.

Author information

Authors and Affiliations

  1. Department of Pathology, North Hospital, University Hospital of Saint-Etienne, 42055, Cedex 2, Saint-Étienne, France

    Georgia Karpathiou, Sirine Hathroubi, Cyril Habougit & Michel Peoc’h

  2. Department of Obstetrics and Gynecology, North Hospital, University Hospital of St-Etienne, Cedex 2, Saint-Étienne, France

    Celine Chauleur

Authors
  1. Georgia Karpathiou
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  2. Celine Chauleur
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  3. Sirine Hathroubi
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  4. Cyril Habougit
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  5. Michel Peoc’h
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Contributions

GK conceived the study. GK and MP designed the study. GK, CC, SH and CH reviewed the clinical files. GK and SH executed the laboratory techniques. All authors were involved in data analysis and interpretation. GK wrote the manuscript. CC, SH, CH and MP critically revised the manuscript. All authors approved the final form.

Corresponding author

Correspondence to Georgia Karpathiou.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Local Ethics Committee of the University Hospital of Saint-Etienne approved the study (IRBN132018/CHUSTE).

Informed consent

The acquisition of written informed consent was waived by the institutional review board given the retrospective nature of the study and the anonymization of all data.

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Cite this article

Karpathiou, G., Chauleur, C., Hathroubi, S. et al. Expression of CD3, PD-L1 and CTLA-4 in mammary and extra-mammary Paget disease. Cancer Immunol Immunother 67, 1297–1303 (2018). https://doi.org/10.1007/s00262-018-2189-x

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  • DOI: https://doi.org/10.1007/s00262-018-2189-x

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