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Int. J. Mol. Sci. 2017, 18(2), 459; doi:10.3390/ijms18020459

Programmed Death Ligand 1 (PD-L1) Tumor Expression Is Associated with a Better Prognosis and Diabetic Disease in Triple Negative Breast Cancer Patients

1
Pathology Unit, Istituto Nazionale Tumori Fondazione “G. Pascale”, via Mariano Semmola, 80131 Napoli, Italy
2
Department of Breast Surgery and Cancer Prevention, Istituto Nazionale Tumori Fondazione “G. Pascale”, via Mariano Semmola, 80131 Napoli, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Dario Marchetti
Received: 28 December 2016 / Revised: 6 February 2017 / Accepted: 15 February 2017 / Published: 21 February 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Triple Negative Breast Cancers (TNBC) subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1) is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value. However, data available in the literature about PD-L1 immunohistochemical expression in breast cancer are often discordant and not uniform, probably for the use of different antibodies clones and the high molecular heterogeneity of the different tumor types. The absence of target therapies, in particular for TNBC, has shifted the clinical attention mainly on the role of PD-L1 in this subtype of breast cancer. In this study, we evaluated tumor and TIL (tumor infiltrating lymphocytes) PDL-1 expression in a series of TNBC, included in Tissue Micro Arrays (TMAs), to define its real prognostic value, optimizing immunohistochemistry method with an “approved for diagnostic assay” antibody. PD-L1 expression directly correlated with proliferation index (Ki-67), glycemia, the presence of diabetes and indirectly with menopausal status, presence of lymph node metastasis and relapse. The analysis of Kaplan–Meier showed that an increased PD-L1 expression was strongly associated with better disease-free survival (DFS) but not correlated with overall survival (OS). Our data confirmed that PD-L1 could be an important marker for prognostic stratification and for planning immune checkpoint inhibitors therapies in patients with TNBC. View Full-Text
Keywords: TNBC; PD-L1; diabetes TNBC; PD-L1; diabetes
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Botti, G.; Collina, F.; Scognamiglio, G.; Rao, F.; Peluso, V.; De Cecio, R.; Piezzo, M.; Landi, G.; De Laurentiis, M.; Cantile, M.; Di Bonito, M. Programmed Death Ligand 1 (PD-L1) Tumor Expression Is Associated with a Better Prognosis and Diabetic Disease in Triple Negative Breast Cancer Patients. Int. J. Mol. Sci. 2017, 18, 459.

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