Breast cancer is the most commonly occurring cancer in women and is the leading cause of cancer death in women in Brazil. Despite being widely studied, it is a disease that is not yet fully understood in its complexity. On the other hand, changes in parkin (parkin RBR E3 ubiquitin protein ligase) expression patterns have been described in several diseases, including breast cancer. Nevertheless, the association of these changes with cancer prognostic and predictive factors remains unclear. Also, parkin regulates APEX1 (apurinic/apyrimidinic endodeoxyribonuclease 1), a protein crucial for repair of oxidized DNA damage, and BCL2L1 (BCL2 like 1), an apoptotic regulator. Both proteins were related to breast cancer.
Immunohistochemical analysis of Parkin, APEX1 and BCL2L1expression were performed in different breast cancer ductal invasive samples from Southern Brazilian patients to characterize their patterns and explore its association with clinical features and disease outcome.Therefore, 112 samples were organized into 15 Tissue Micro Arrays. The samples were classified in four molecular subtypes based on clinicopathological criteria (46 Luminal B, 24 Luminal A, 24 Basal and 18 HER2). These samples were obtained from Hospital Nossa Senhora das Graças (Curitiba, PR, Brazil) patients who were followed from 5 to 18 years.
Parkin, APEX1 and BCL2L1 showed different expression patterns between the subtypes assessed. While in Luminal A and B APEX1 expression was increased, parkin expression was higher among Basal and HER2 subtypes. BCL2L1 expression was increased mainly in HER2 subtype. When regarding to estrogen (ER) and progesterone (PR) receptors, APEX1 was more expressed in ER/PR-positive samples, whereas Parkin and BCL2L1 in negative ones. No such difference was observed considering only HER2. BCL2L1 expression pattern was significantly associated with disease-free survival time independent of molecular subtypes, lymph node status and tumor size (p = 0.020). The higher the expression levels of BCL2L1, the shorter the disease-free survival time.
The expression of BCL2L1 is direclty associated with relapse of ductal invasive breast tumors, independently of other clinical variables.
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Legal entity responsible for the study
Pontifícia Universidade Católica do Paraná (PUCPR).
Has not received any funding.
All authors have declared no conflicts of interest.