Immunohistochemical expressions of SQSTM1/p62, Beclin-1, and SOX4 in infiltrating duct carcinoma of the breast

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Abstract

Background

Breast cancer is the most common tumor and the second cause of death in women worldwide. Study of the molecular pathogenesis of breast cancer enables adequate management that will help to decrease its fatality. Autophagy is a lysosomal degradation process that removes damaged organelles to maintain cellular homeostasis. The role of autophagy in cancer is complicated; it may act as an inhibitor or a stimulator for cancer depending on the type of cancer. Thirty-four proteins have been detected in human cells and had 34 counterparts; yeast cells control this process. Beclin-1 is the human counterpart of the yeast Apg6/Vps30 gene; it plays an important role in autophagy. SQSTM1/p62 (Sequestosome-1) is an adapter protein that controlled the delivery of ubiquitin-bound cargo to the autophagosome. Epithelial–mesenchymal transition is the process by which epithelial cells alter their characteristics such as loss of cell–cell adhesion and downregulation of epithelial markers, followed by acquisition of mesenchymal characteristics such as increasing mobility, invasive power, and elevated resistance to apoptosis. The sex-determining region Y (SRY) box (SOX) family comprises 20 conserved transcription factors. SOX4, a member of the C subgroup of the SOX family, is characterized by an HMG box domain that binds the minor groove of the DNA helix.

Aim of the work

This study aimed to detect immunohistochemical expressions of SQSTM1/p62 and Beclin-1, comparing their expressions with each other and with SOX4 expression in infiltrating duct carcinoma of the breast to determine the relation between their expressions and prognosis of that type of cancer.

Patients and methods

Immunohistochemical expressions of SQSTM1/p62, Beclin-1, and SOX4 were evaluated in sections from 60 paraffin blocks of invasive ductal carcinoma (IDC) of the breast. The relationship between their level of expressions and prognosis of the patients was analyzed.

Results

The expression of SQSTM1/p62, in IDC was significantly positively correlated with size, grade, stage, local recurrence of the tumor, lymph node, and distant metastasis (P<0.001), the expression of Beclin-1 in IDC was significantly negatively correlated with size of the tumor, grade, stage, local recurrence, lymph node, and distant metastasis (P<0.001), and the expression of SOX4 in IDC was significantly positively correlated with stage, local recurrence, lymph node and distant metastases (P<0.001), and size and grade of the tumor (P=0.002). High SQSTM1/p62, SOX4 and low Beclin-1 expression were strongly correlated with worse 3-year overall survival (P<0.001) and local recurrence-free survival (P=0.007, 0.003, and 0.035, respectively).

Conclusion

High levels of expression of SQSTM1/p62 and SOX4 are markers of poor prognosis, whereas high levels of expression of Beclin-1 are a marker of good prognosis in IDC.

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