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

Jaudah Al-Maghrabi, Kaltoom Al-Sakkaf, Imtiaz Ahmad Qureshi, Nadeem Shafique Butt, Lila Damnhory, Mohamed Elshal, Basim Al-Maghrabi, Alia Aldahlawi, Sawsan Ashoor, Barry Brown, Pauline Dobson, Mohamad Nidal Khabaz

Full text: http://dx.doi.org/10.1016/j.anndiagpath.2017.05.012

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Abstract

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.

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