AMPK expression patterns are significantly associated with poor prognosis in breast cancer patients

被引:14
作者
Al-Maghrabi, Jaudah [1 ]
Al-Sakkaf, Kaltoom [2 ]
Qureshi, Imtiaz Ahmad [3 ]
Butt, Nadeem Shafique [4 ]
Damnhory, Lila [2 ]
Elshal, Mohamed [5 ]
Al-Maghrabi, Basim [6 ]
Aldahlawi, Alia [7 ]
Ashoor, Sawsan [8 ]
Brown, Barry [9 ]
Dobson, Pauline [9 ]
Khabaz, Mohamad Nidal [3 ]
机构
[1] King Abdulaziz Univ, Dept Pathol, Fac Med, Jeddah, Saudi Arabia
[2] King Abdulaziz Univ, Dept Med Lab Technol, Fac Appl Med Sci, Jeddah, Saudi Arabia
[3] King Abdulaziz Univ, Dept Pathol, Rabigh Fac Med, POB 80205, Jeddah 21589, Saudi Arabia
[4] King Abdulaziz Univ, Dept Family & Community Med, Rabigh Fac Med, Jeddah, Saudi Arabia
[5] King Abdulaziz Univ, Dept Biol Sci, Fac Sci, Jeddah, Saudi Arabia
[6] King Abdulaziz Univ, Fac Med, Jeddah, Saudi Arabia
[7] King Abdulaziz Univ, Immunol Unit, King Fahad Res Med Ctr, Jeddah, Saudi Arabia
[8] KAU Hosp, Dept Radiol, Jeddah, Saudi Arabia
[9] Univ Sheffield, Dept Human Metab, Sheffield, S Yorkshire, England
关键词
AMP-activated protein kinase; AMPK; Breast Cancer; Immunohistochemistry; ACTIVATED PROTEIN-KINASE; CELL METABOLISM; AUTOPHAGY; PHOSPHORYLATION; DEHYDROGENASE; INHIBITION; GLUCOSE;
D O I
10.1016/j.anndiagpath.2017.05.012
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Many investigators have examined the functions of AMP-activated protein kinase (AMPK) in cancer biology and its anti-neoplastic features in cancer models. The goal of this research is to assess the association of the immunohistochemical expression of AMPK in human mammary tumours with the clinical data of breast cancer patients. 449 cases of previously diagnosed breast cancer, and 27 tissue samples of fibroadenomas and normal breast were utilized for detection of AMPK expression using tissue microarrays and immunohistochemistry. Brownish nuclear and cytoplasmic staining were present in epithelial cells and stromal cells in 333 (74.16%) and 348 (77.5%) cancer cases respectively indicating AMPK expression. Twenty two (81.48%) control cases showed AMPK immunoexpression in both epithelial and stromal cells. Significant statistical association has been found between advanced stages of breast cancer and increased intensity of AMPK immunostaining only in epithelial cells (p-value = 0.0001). Histotypes have been correlated with AMPK immunostaining in epithelial cells only (p value = 0.029). Low AMPK immunostaining scores were more dominant in DCIS, ductal and mixed type's ductal and mucinous histotypes, while high intense staining was more common in the lobular type. Furthermore, breast tumour cases with lymph node metastases showed significant AMPK expression in both epithelial and stromal cells (p-value = 0.0001 and p-value = 0.026). Low scores of AMPK immunostaining were common in breast cancer cases with positive vascular invasion (p-value = 0.007) and disease recurrence (p-value = 0.008). No significant differences in survival behavior distributions were observed for the different categories of AMPK immunostaining in epithelial and stromal cells. In conclusion, our results showed decreased AMPK expression in breast cancer in comparison with the control group. AMPK expression was significantly correlated with some clinicopathological factors like advanced stage, lymph node involvement, vascular invasion and disease recurrence which give indications for poor clinical outcomes. Immunohistochemical staining of AMPK protein is a valuable method which could predict cases of breast cancer with poor prognosis.
引用
收藏
页码:62 / 67
页数:6
相关论文
共 43 条
[1]  
Al-Zahrani W, 2015, CANC INCIDENCE REPOR, V1
[2]   LKB1-dependent signaling pathways [J].
Alessi, Dario R. ;
Sakamoto, Kei ;
Bayascas, Jose R. .
ANNUAL REVIEW OF BIOCHEMISTRY, 2006, 75 :137-163
[3]  
American Cancer Society, 2014, CAN FACTS FIG 2014, V2014, P1
[4]   Predominant α2/β2/γ3 AMPK activation during exercise in human skeletal muscle [J].
Birk, J. B. ;
Wojtaszewski, J. F. P. .
JOURNAL OF PHYSIOLOGY-LONDON, 2006, 577 (03) :1021-1032
[5]   Endocrine-related cancers and the role of AMPK [J].
Brown, Kristy A. ;
Samarajeewa, Nirukshi U. ;
Simpson, Evan R. .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2013, 366 (02) :170-179
[6]   Cancer Cell Metabolism: One Hallmark, Many Faces [J].
Cantor, Jason R. ;
Sabatini, David M. .
CANCER DISCOVERY, 2012, 2 (10) :881-898
[7]   Targeting GLUT1 and the Warburg Effect in Renal Cell Carcinoma by Chemical Synthetic Lethality [J].
Chan, Denise A. ;
Sutphin, Patrick D. ;
Nguyen, Phuong ;
Turcotte, Sandra ;
Lai, Edwin W. ;
Banh, Alice ;
Reynolds, Gloria E. ;
Chi, Jen-Tsan ;
Wu, Jason ;
Solow-Cordero, David E. ;
Bonnet, Muriel ;
Flanagan, Jack U. ;
Bouley, Donna M. ;
Graves, Edward E. ;
Denny, William A. ;
Hay, Michael P. ;
Giaccia, Amato J. .
SCIENCE TRANSLATIONAL MEDICINE, 2011, 3 (94)
[8]   Functional characterization of AMP-activated protein kinase signaling in tumorigenesis [J].
Cheng, Ji ;
Zhang, Tao ;
Ji, Hongbin ;
Tao, Kaixiong ;
Guo, Jianping ;
Wei, Wenyi .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2016, 1866 (02) :232-251
[9]   Therapeutic targets in cancer cell metabolism and autophagy [J].
Cheong, Heesun ;
Lu, Chao ;
Lindsten, Tullia ;
Thompson, Craig B. .
NATURE BIOTECHNOLOGY, 2012, 30 (07) :671-678
[10]   The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth [J].
Christofk, Heather R. ;
Vander Heiden, Matthew G. ;
Harris, Marian H. ;
Ramanathan, Arvind ;
Gerszten, Robert E. ;
Wei, Ru ;
Fleming, Mark D. ;
Schreiber, Stuart L. ;
Cantley, Lewis C. .
NATURE, 2008, 452 (7184) :230-U74