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Autophagy-related molecules, light chain 3B, p62, and beclin 1, as prognostic markers in triple-negative breast cancer

Abdelbary, Eman H.a; Abdelaziz Ibrahim, Doaaa; Abdelgawad, Mohamedb

Egyptian Journal of Pathology: July 2017 - Volume 37 - Issue 1 - p 8–16
doi: 10.1097/01.XEJ.0000515962.69459.44
ORIGINAL ARTICLES
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Background and aim Triple-negative breast cancer (TNBC) is associated with aggressive behavior and poor clinical outcome. Therefore, identification of biomarkers predicting prognosis may help to improve the clinical outcome of TNBC. Autophagy is a process of lysosomal degradation and recycling of intracellular components. It plays an important role in normal cells as well as in malignant cells.

The aim of this study was to investigate the pattern of expression of autophagy-related molecules, light chain 3B (LC3B), p62, and beclin 1, their relationship with clinicopathological features, and their prognostic value in TNBC patients.

Materials and methods LC3B, p62, and beclin 1 proteins were assessed immunohistochemically in 28 cases of TNBC, and their capacity to predict overall survival and disease-free survival was evaluated.

Results LC3B protein expression showed a significant direct relation with nodal stage (P=0.005) and a near-significant relation with tumor size (P=0.057). Nuclear p62 protein expression was inversely related to tumor size (P=0.019). However, cytoplasmic p62 positivity was directly related to tumor size and nodal metastasis (P=0.002 and 0.001, respectively). Nuclear beclin 1 reactivity was not related to any of the clinicopathological features of the cases. However, cytoplasmic expression of beclin 1 was inversely associated with nodal stage and tumor size (P=0.001 and 0.052, respectively). A significant inverse relationship was noticed between cytoplasmic beclin 1 and cytoplasmic p62 as well as LC3B protein expression (P=0.018 and <0.001, respectively), whereas LC3B immunoreactivity was directly associated with p62 cytoplasmic protein expression (P=0.047). LC3B, loss of cytoplasmic beclin 1, and cytoplasmic p62 proteins expression were associated with shorter disease-free survival (P=0.004, <0.001, and 0.024, respectively). Poor overall survival was related to loss of beclin 1 protein expression and LC3B positivity (P=0.023 and 0.059, respectively).

Conclusion High cytoplasmic LC3B and p62, with low beclin 1 protein expressions could be suggested as markers of aggressive behavior and shorter survival in TNBC patients.

Departments of aPathology

bClinical Oncology and Nuclear Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Correspondence to Eman H. Abdelbary, MD, Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt Tel: +0552307830; fax: +0552307830; e-mail: em_bary@hotmail.com

Received August 1, 2016

Accepted January 1, 2017

©2017Egyptian Journal of Pathology
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