Immune checkpoints in aggressive breast cancer subtypes

• Published in: Neoplasma 2016, Vol.63 (5), p.768-773
• Main Authors: Zawlik, I, Gablo, N, Szymanska, B, Pawlowska, Z, Chudobinski, C, Chalubinska-Fendler, J, Morawiec, Z, Zielinska-Blizniewska, H, Morawiec-Sztandera, A, Kolacinska, A
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Biomarkers, Tumor - metabolism; Female; Humans; Middle Aged; Prognosis; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - metabolism; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; RNA, Messenger - genetics; Triple Negative Breast Neoplasms - classification; Triple Negative Breast Neoplasms - immunology; Triple Negative Breast Neoplasms - pathology
• ISSN: 0028-2685
• DOI: 10.4149/neo_2016_514

Immune checkpoints are molecules referred to inhibitory pathways in the immune system that play a pivotal role in prevention of autoimmunity and oncogenesis. The aim of the study was to evaluate expression levels of selected immune checkpoints- PD-1 (programmed cell death protein 1), and PD-L1 (programmed cell death 1 ligand 1) in breast cancer patients, suitable for breast conservation and sentinel node biopsy and determine their associations with clinicopathological factors.Expression of the genes coding for PD-1 and PD-L1 was analyzed in formalin-fixed paraffin-embedded specimens using real-time PCR. mRNA expression levels were determined using beta actin (ACTB) as an endogenous control. There was a trend towards significance between higher PD-1 and PD-L1 levels in triple negative breast cancers (p=0.1). Higher PD-L1 expression was also found in aggressive breast cancer subtypes e.g. triple negative and HER2 (human epidermal growth factor receptor 2) -positive as compared with subtypes with better prognosis such as luminal A and luminal BHER2-negative (p=0.05). There was a trend towards significance in higher PD-1 levels in triple negative and HER-2 positive breast cancers (p=0.1). A statistically significant difference was found between PD-L1 expression and tumor grade (p=0.01). Elevated PD-L1 levels were noted in G3 tumors. Immunogenicity appears to be gaining importance in triple negative and HER2-positive molecular subtypes of breast cancer, and the results in this study provide a basis for further investigation into the role of immune checkpoints in breast cancer.