PD-1, PD-L1 and CTLA-4 in pregnancy-related – and in early-onset breast cancer: A comparative study

Balázs Ács, Lilla Madaras, A. Tőkés, Attila Kristóf Kovács, Erzsébet Kovács, Magdolna Ozsvári-Vidákovich, Ádám Karászi, Ede Birtalan, Magdolna Dank, A. Szász, J. Kulka

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8 Citations (Scopus)

Abstract

Purpose We aimed to compare the immunohistochemical expression of PD-1, PD-L1 and CTLA-4 of pregnancy-related breast cancer (PRBC) and early onset non-PRBC (YWBC), and their prognosis prediction potential was correlated to that of conventional clinicopathological factors. Methods Twenty-one PRBC cases were paired with 21 YWBC in this matched case-control study. Immune-checkpoint markers (ICM) were evaluated with immunohistochemistry (IHC) on whole slides using the following antibodies: PD-1 (NAT-105), PD-L1 (28-8) and CTLA-4 (F-8). IHC score was defined as the percentage of positive cells, assessed separately among tumor cells, intratumoral lymphocytes and peritumoral lymphocytes. Results The optimal threshold of PD-L1 expression of tumor cells occurred at 10% for overall survival (OS, AUC = 0.847, p = 0.009), and at 1% for disease-free survival (DFS, AUC = 0.795, p = 0.010). For PD-L1 expression on intratumoral lymphocytes, the optimal cut-off was 1% (AUC = 0.763, p = 0.048). Considering PD-1, PD-L1 and CTLA-4 expression, no significant difference occurred between PRBC and YWBC (p > 0.05 for all comparisons). PD-1, PD-L1 expressed on peritumoral lymphocytes and CTLA-4 failed, but PD-L1 expressed on tumor cells and on intratumoral lymphocytes was suitable to distinguish patient cohorts with different OS and DFS (p ≤ 0.011 for all comparisons). Higher PD-L1 expression was associated with poor prognosis. PD-L1 expressed on tumor cells represented an independent association with OS (p = 0.023) and DFS (p = 0.032). Conclusions Our results suggest that PRBC and YWBC do not differ in the expression of PD-1, PD-L1 and CTLA-4. However, our findings emphasize the relevance of PD-L1 expression in early-onset breast cancer, as an independent negative predictor of prognosis.

Original languageEnglish
Pages (from-to)69-77
Number of pages9
JournalBreast
Volume35
DOIs
Publication statusPublished - Oct 1 2017

Keywords

  • CTLA-4
  • PD-1
  • PD-L1
  • Pregnancy-related breast cancer
  • Prognosis
  • Young women with breast cancer

ASJC Scopus subject areas

  • Surgery

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    Ács, B., Madaras, L., Tőkés, A., Kovács, A. K., Kovács, E., Ozsvári-Vidákovich, M., Karászi, Á., Birtalan, E., Dank, M., Szász, A., & Kulka, J. (2017). PD-1, PD-L1 and CTLA-4 in pregnancy-related – and in early-onset breast cancer: A comparative study. Breast, 35, 69-77. https://doi.org/10.1016/j.breast.2017.06.013