High expression of LC3B is associated with progression and poor outcome in triple-negative breast cancer

Microtubule-associated protein 1 light chain 3B (LC3B) was involved in autophagosome formation and had been as a marker of autophagy which played an important role in the development of breast cancer. The purpose of this study was to explore the level of LC3B expression in four stages of triple-negative breast cancer (TNBC) and to evaluate the prognostic significance of LC3B expression in TNBC. The ultimate aim was to identify the new factor that could be useful in predicting clinical behavior of TNBC. We evaluated the expression level of LC3B protein in four kinds of TNBC tissue samples, including intraductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) without metastases, IDC with lymph node metastases (LNM), and IDC with distant metastases (DM). Hundred and four primary TNBC patients were involved in present study, and the expression level of LC3B protein was assessed by immunohistochemistry. Medical records of these patients were reviewed, and the clinicopathological analysis was performed. High expression of LC3B was observed in 7.7 % of DCIS (1 of 13 cases), 16.2 % of IDC (6 of 37 cases), 35.7 % of LNM (15 of 42 cases), and 58.3 % of DM (7 of 12 cases). LC3B high expression was significantly associated with tumor size (P = 0.028), lymph node metastasis (P = 0.002), and Ki-67 expression (P = 0.047). LC3B high expression patients showed poorer DFS and OS rates compared with LC3B low expression patients (P = 0.024, and P = 0.047, respectively). Multivariate analyses confirmed that high LC3B expression was an independent and significant factor for predicting the poor outcome of TNBC patients. These preliminary results demonstrated that high LC3B expression was associated with lymph node and distant metastasis. Furthermore, high LC3B protein expression was correlated with shorter survival in patients with triple-negative breast carcinoma. These findings provided preliminary evidence for the function of LC3B on the progression of TNBC and suggested LC3B was a useful marker in prognostic evaluation for patients with TNBC.

[1]  A. Giatromanolaki,et al.  LC3A-Positive “Stone-Like” Structures in Cutaneous Squamous Cell Carcinomas , 2011, The American Journal of dermatopathology.

[2]  A. Kimchi,et al.  The paradox of autophagy and its implication in cancer etiology and therapy , 2009, Apoptosis.

[3]  A. Tutt,et al.  Triple negative tumours: a critical review , 2007, Histopathology.

[4]  A. Harris,et al.  Prognostic relevance of light chain 3 (LC3A) autophagy patterns in colorectal adenocarcinomas , 2010, Journal of Clinical Pathology.

[5]  R. Gelber,et al.  Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011 , 2011, Annals of oncology : official journal of the European Society for Medical Oncology.

[6]  A. Ochiai,et al.  Enhancer of zeste homolog 2 downregulates E‐cadherin by mediating histone H3 methylation in gastric cancer cells , 2008, Cancer science.

[7]  Kevin Bray,et al.  Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. , 2006, Cancer cell.

[8]  Daniel J Klionsky,et al.  Development by self-digestion: molecular mechanisms and biological functions of autophagy. , 2004, Developmental cell.

[9]  M. Remacle,et al.  Predictive value of the fraction of cancer cells immunolabeled for proliferating cell nuclear antigen or Ki67 in biopsies of head and neck carcinomas to identify lymph node metastasis: Comparison with clinical and radiologic examinations , 2003, Head & neck.

[10]  M. Czaja.  Functions of autophagy in hepatic and pancreatic physiology and disease. , 2011, Gastroenterology.

[11]  Isei Tanida.  Autophagy basics , 2011, Microbiology and immunology.

[12]  Govind Bhagat,et al.  Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. , 2003, The Journal of clinical investigation.

[13]  Y. Atomi,et al.  Autophagy is activated in colorectal cancer cells and contributes to the tolerance to nutrient deprivation. , 2007, Cancer research.

[14]  A. Giatromanolaki,et al.  Autophagy in endometrial carcinomas and prognostic relevance of 'stone-like' structures (SLS): What is destined for the atypical endometrial hyperplasia? , 2011, Autophagy.

[15]  R. Camp,et al.  Punctate LC3B Expression Is a Common Feature of Solid Tumors and Associated with Proliferation, Metastasis, and Poor Outcome , 2011, Clinical Cancer Research.

[16]  D. Klionsky,et al.  Biochemical methods to monitor autophagy-related processes in yeast. , 2008, Methods in enzymology.

[17]  G. Mills,et al.  Monitoring autophagy in glioblastoma with antibody against isoform B of human microtubule-associated protein 1 light chain 3 , 2008, Autophagy.

[18]  V. Karantza,et al.  Role of Autophagy in Breast Cancer , 2007, Autophagy.

[19]  N. Mizushima,et al.  Physiological role of autophagy as an intracellular recycling system: with an emphasis on nutrient metabolism. , 2010, Seminars in cell & developmental biology.

[20]  J. Zhao,et al.  Characteristics and prognosis for molecular breast cancer subtypes in Chinese women , 2009, Journal of surgical oncology.

[21]  S. Waguri,et al.  Measurement of autophagy in cells and tissues. , 2010, Methods in molecular biology.

[22]  Mei Lan Tan,et al.  Immunohistochemical expression of MAP1LC3A and MAP1LC3B protein in breast carcinoma tissues , 2009, Journal of clinical laboratory analysis.

[23]  Y. Doki,et al.  LC3, an autophagosome marker, is highly expressed in gastrointestinal cancers. , 2008, International journal of oncology.

[24]  M. Kojima,et al.  Autophagy is activated in pancreatic cancer cells and correlates with poor patient outcome , 2008, Cancer science.

[25]  Jun O. Liu,et al.  Post-translational Modifications of Three Members of the Human MAP1LC3 Family and Detection of a Novel Type of Modification for MAP1LC3B* , 2003, Journal of Biological Chemistry.

[26]  J. Debnath,et al.  Induction of autophagy during extracellular matrix detachment promotes cell survival. , 2007, Molecular biology of the cell.

[27]  John L Cleveland,et al.  Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes , 2008, Autophagy.

[28]  P. Codogno,et al.  Regulation and role of autophagy in mammalian cells. , 2004, The international journal of biochemistry & cell biology.

[29]  S. Emr,et al.  Autophagy as a regulated pathway of cellular degradation. , 2000, Science.