Expression of p-AMPK is associated with hormone receptor phenotypes and lymph node metastasis in breast cancer
Mohamad Nidal Khabaz, Kaltoom Al-Sakkaf, Imtiaz Ahmad Qureshi, Nadeem Shafique Butt, Lila Damnhory, Mohamed Elshal, Basim Al-Maghrabi, Alia Aldahlawi, Sawsan Ashoor, Barry Brown, Pauline Dobson, Jaudah Al-Maghrabi
Many studies have investigated the role of phosphorylated AMP-activated protein kinase (p-AMPK) in cancer tumorigenesis and its antineoplastic effects in cancer models. The aim of this study was to examine the association of p-AMPK immunohistochemical expression with the clinicopathological parameters in breast cancer. Methods: 449 cases of previously diagnosed breast cancer, and 27 tissue samples of fibroadenomas and normal breast were utilized for detection of p-AMPK expression using tissue microarrays and immunohistochemistry. Results: Nuclear and cytoplasmic immunoexpression of p-AMPK was identified in 374 (83.3%) of breast cancer and 25 (92.6%) control cases. Hormone receptor phenotypes are significantly associated with p-AMPK staining only in epithelial cells (P-value = 0.033); the proportions of ER+ PR- HER2-hormone receptor phenotype were significantly higher in positive p-AMPK staining epithelial cells. Loss of progesterone receptor (PR) expression was noticeable in breast tumors with positive p-AMPK stromal cells (P-value = 0.043). Histotype of breast cancer is significantly associated with p-AMPK staining in stromal cells only; positive p-AMPK staining was more prevalent in DCIS and ductal histotypes (P-value = 0.032). Lymph node involvement was also significantly associated with p-AMPK immunostaining in both epithelial cells and stromal cells (P-value = 0.037 and P-Value = 0.042 respectively). No significant differences in survival behavior were observed and no significant associations were detected with tumor size, grade of disease, stage, vascular invasion, margins involvement and disease recurrence. Conclusions: Our results showed a slight decrease in p-AMPK expression in breast cancer in comparison with control group. Expression of p-AMPK could be a useful marker in the diagnosis and prognosis of some types of breast cancer with certain hormone receptor phenotype and lymph node involvement.