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Prognostic Role of Immune Markers in Triple Negative Breast Carcinoma

  • Original Article
  • Published:
Pathology & Oncology Research

Abstract

Tumor immune microenvironment (TIME) is a significant prognostic parameter for triple negative breast carcinomas (TNBC) due to being a target for immunotherapeutic agents and its essential role during the cancer immunoediting process. In this study, CD8, FOXP3, CD163, PD-L1/SP142 and PD-L1/SP263 antibodies were examined in a sample of 51 TNBC cases. Patients who received neoadjuvant therapy were excluded. CD8, FOXP3 and CD163 antibodies were evaluated separately in intratumoral area (ITA) and tumor stroma (TS). PD-L1 status was also examined in tumor cells (TC) and immune cells (IC) using both SP142 and SP263 antibodies. In multivariate Cox regressions, the only antibody that was found to be significantly associated with survival was SP142. SP142-positivity in TC and IC was related to increased overall survival. Higher CD163 expression in ITA and SP263-positivity in IC were associated with younger age. Lymphatic/angioinvasion was more frequent in cases with negative/low CD8 and FOXP3 expressions. Moreover, metastatic axillary lymph node(s) was associated with negative/low FOXP3 expression in TS. CD8, FOXP3, CD163, SP142 and SP263 expressions were positively correlated with each other, except a mild discordance caused by CD163 in ITA. Although PD-L1 status with both SP142 and SP263 antibodies were concordant in the majority of cases, 33.3% and 13.7% of the cases showed SP142-negative/SP263-positive pattern in TC and IC respectively. In conclusion, we suggest that composition, density and localization of the immune cells and the check point molecules are important prognostic parameters in TNBC. Immunohistochemistry can be used as an accessible and less expensive tool to demonstrate TIME.

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Availability of Data and Material

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgments

The authors thank Ms. Elif Ugurlu and Mr. Mucahit Ozkelle for technical support during sectioning and performing immunohistochemistry.

Funding

This study was funded by the Scientific Research and Projects Board of the Marmara University, Istanbul, Turkey (Grant number: SAG-C-TUP-131217-0659).

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Authors and Affiliations

  1. Department of Pathology, Marmara University School of Medicine, Pendik Research and Training Hospital, Istanbul, Turkey

    Hulya Sahin Ozkan & Handan Kaya

  2. Department of General Surgery, Marmara University School of Medicine, Pendik Research and Training Hospital, Istanbul, Turkey

    Mustafa Umit Ugurlu

  3. Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Pendik Research and Training Hospital, Istanbul, Turkey

    Perran Fulden Yumuk

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  1. Hulya Sahin Ozkan
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  2. Mustafa Umit Ugurlu
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  3. Perran Fulden Yumuk
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  4. Handan Kaya
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed and the first draft of the manuscript was written by Hulya Sahin Ozkan. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. The role of the each author in this paper as follows:

Conceptualization: Hulya Sahin Ozkan, Handan Kaya.

Methodology: Hulya Sahin Ozkan.

Formal analysis and investigation: Hulya Sahin Ozkan.

Data collection - histopathological and immunohistochemical: Hulya Sahin Ozkan.

Data collection - clinical: Mustafa Umit Ugurlu, Perran Fulden Yumuk.

Writing - original draft preparation: Hulya Sahin Ozkan.

Writing - review and editing: Mustafa Umit Ugurlu, Perran Fulden Yumuk, Handan Kaya.

Funding acquisition: Hulya Sahin Ozkan, Handan Kaya.

Resources: Hulya Sahin Ozkan, Handan Kaya.

Supervision: Handan Kaya.

Corresponding author

Correspondence to Hulya Sahin Ozkan.

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Conflicts of Interest/Competing Interests

The authors declare that they have no conflicts of interest and/or competing interests.

Ethics Approval

The study protocols were approved by the Ethical Board of the Marmara University Medical School, Istanbul, Turkey (Protocol number: 09.2017.665).

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Code Availability

R code of the statistical analyses is available from the corresponding author on reasonable request.

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Sahin Ozkan, H., Ugurlu, M.U., Yumuk, P.F. et al. Prognostic Role of Immune Markers in Triple Negative Breast Carcinoma. Pathol. Oncol. Res. 26, 2733–2745 (2020). https://doi.org/10.1007/s12253-020-00874-4

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  • DOI: https://doi.org/10.1007/s12253-020-00874-4

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