Phosphorylated AMP-activated protein kinase expression is significantly associated with poor clinical outcomes in bladder carcinoma patients

Jaudah Al-maghrabi, Imtiaz Ahmad Qureshi, Nadeem Shafique Butt, Mohamad Nidal Khabaz

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Abstract

The phenotype of p-AMPK has been suggested as a possible marker for diagnosis and/or prognosis in tumors located in different organs. Nonetheless, there are conflicts among the outcomes found in several tumors, and little is proven concerning the correlation between the phenotype of p-AMPK and its clinical significance in urinary bladder carcinomas. Therefore, this research will define the p-AMPK expression patterns, and study the relationship between this pattern of expression, in a panel of urinary bladder carcinomas compared to normal tissues, and clinicopathological features to determine the clinical relevance and the function of p-AMPK in the evolution of bladder cancer. Furthermore, this study will evaluate p-AMPK expression as a diagnostic marker and prognosticator of long term overall survival in bladder cancer patients. This study will utilize the p-AMPK monoclonal antibody using the immunohistochemistry staining standard protocol to identify the location and expression pattern of p-AMPK, which will be graded with respect to the estimated percentage of tumor cells with positive and relative intense stain. 128 cases of urinary bladder carcinoma and 24 non-cancerous bladder tissue samples were employed for the determination of p-AMPK phenotypes applying immunohistochemical staining on tissue microarrays slides. A high score of nuclear p-AMPK immunoexpression has been found in 104 (81.3%) bladder cancer cases, while 24 (100%) control cases showed p-AMPK immunoreactivity. Strong p-AMPK immunohistochemical staining in both epithelial cells and stromal cells has been significantly linked with vascular invasion (p-value = 0.002 and p-value = 0.011 respectively). Lymph node metastasis showed significant association with p-AMPK expression in tumor epithelial cells (p-value = 0.030). The odds of low expression in epithelial cells for a positive lymph node are 3.21 times as great as the odds of low expression in epithelial cells for a negative lymph node. Our findings recommend p-AMPK as a useful biomarker in determining the prognosis of bladder cancer. These preliminary findings suggest that p-AMPK may be a valuable tissue biomarker for predicting a poor prognosis in bladder cancer.

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