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Breast. 2017 Oct;35:69-77. doi: 10.1016/j.breast.2017.06.013. Epub 2017 Jun 23.

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

Author information

1
2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary. Electronic address: acs.balazs.se@gmail.com.
2
2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary. Electronic address: madaras.lilla@med.semmelweis-univ.hu.
3
MTA-SE Tumor Progression Research Group, 2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary. Electronic address: tokesa1972@yahoo.co.uk.
4
2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary. Electronic address: kovacs.attila@med.semmelweis-univ.hu.
5
2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary. Electronic address: azumahne@gmail.com.
6
2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary. Electronic address: magdus.vidak@gmail.com.
7
2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary. Electronic address: adam.karaszi@gmail.com.
8
Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Semmelweis University, 36 Szigony utca, Budapest, 1083, Hungary. Electronic address: birtalanede@gmail.com.
9
Cancer Center, Semmelweis University, Tömő utca 25-29, Budapest, 1083, Hungary. Electronic address: magdolna.dank@gmail.com.
10
2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary; Cancer Center, Semmelweis University, Tömő utca 25-29, Budapest, 1083, Hungary. Electronic address: cac@korb2.sote.hu.
11
2nd Department of Pathology, Semmelweis University, 93 Üllői út, Budapest, 1091, Hungary. Electronic address: kulka.janina@med.semmelweis-univ.hu.

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.

KEYWORDS:

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

PMID:
28651116
DOI:
10.1016/j.breast.2017.06.013
[Indexed for MEDLINE]

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