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Open Access Highly Accessed Research article

Expression of autophagy-related protein beclin-1 in malignant canine mammary tumors

Jing-Lan Liu1, Kai-Chian Chang1, Chun-Chih Lo1, Pei-Yi Chu12* and Chen-Hsuan Liu3*

Author Affiliations

1 Department of Pathology, St. Martin De Porres Hospital, No. 565, Section 2, Daya Road, Chiayi, 60069, Taiwan

2 School of Medicine, Fu-Jen Catholic University, No. 510, Zhongzheng Road, Xinzhuang Dist., New Taipei City, 24205, Taiwan

3 Graduate Institute of Molecular and Comparative Pathobiology, School of Veterinary Medicine, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei, 10617, Taiwan

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BMC Veterinary Research 2013, 9:75  doi:10.1186/1746-6148-9-75

Published: 11 April 2013

Abstract

Background

Autophagy is a self-catabolic mechanism that degrades unnecessary cellular components through lysosomal enzymes. Beclin-1, an autophagy-related protein, establishes the first connection between autophagy and tumorigenesis. The purpose of this study is to assess the Beclin-1 expression pattern and to determine its prognostic significance in patients with malignant canine mammary tumor (CMT).

Results

We examined Beclin-1 expression in 70 cases of malignant CMTs by immunohistochemistry. Cytoplasmic Beclin-1 expression was significantly weaker in cancer cells than in nearby normal mammary glands (p < 0.001). Low cytoplasmic expression (57.14%) was associated with older age, lower degree of tubular formation, increased mitotic activity, higher histologic grade, and extensive necrosis. Low nuclear expression (40%) was connected with older age, lower degree of tubular formation, extensive necrosis, and negative for Her2/neu overexpression. Univariate survival analysis showed that Beclin-1 cytoplasmic expression was a poor prognostic factor for overall survival rate (p < 0.001). Multivariate survival analysis demonstrated that Beclin-1 cytoplasmic expression is an independent prognostic factor (p = 0.016).

Conclusions

Loss of Beclin-1 is associated with aggressive clinicopathologic features and poor overall survival. The results suggest that Beclin-1 plays an important role in tumor progression of malignant CMTs.

Keywords:
Autophagy; Beclin-1; Canine mammary tumor; Immunohistochemistry