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.
Cardiac involvement of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is recognized extremely rarely. In addition, most CLL/SLL patients with heart infiltration are asymptomatic. In this review, we present the results of a literature search for English language articles concerning CLL/SLL or Richter transformation with symptomatic cardiac involvement. In total, 18 well-described cases with CLL/SLL and heart infiltration were identified. Only three patients were not diagnosed with CLL/SLL before the cardiac manifestation. In other patients, cardiac CLL/SLL was diagnosed between 5 months and 20 years from CLL/SLL diagnosis. All patients in these series had a diagnosis of secondary cardiac CLL/SLL. In addition, we identified four reported cases with Richter transformation in the heart. The treatment of patients with CLL/SLL and cardiac infiltration is variable and depends on the previous history and clinical characteristics of heart infiltration. In addition, no recommendations exist on how to treat patients with CLL/SLL and cardiac involvement.
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