Clinicopathological significance of c-MET and HER2 altered expression in bladder cancer
Engy Mohammed Naguib1, E F Ismail2, D I Badran2
1Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt. engynaguib@med.suez.edu.eg.
Background:
Tumor recurrence or metastasis after surgery is a significant factor influencing bladder cancer (BC) prognosis. Novel molecular biomarkers are necessary to determine each patient's specific outcome because current biomarkers have limited power for predicting prognosis. The proto-oncogene MET encodes c-MET, a tyrosine kinase receptor. When c-MET attaches to its ligand, it triggers several steps in the signal transduction cascade that control cell survival, proliferation, and invasion. c-MET is overexpressed in several carcinomas. The HER2 gene encodes another receptor tyrosine kinase (RTK). HER2 overexpression is linked to altered proliferation and increased aggressiveness in several malignancies. Identifying crosstalk partners of RTKs implicated in bladder cancer development may have a unique role in predicting aggressiveness. This study explored the expression status of c-MET and HER2 in human BC and their clinical significance in disease outcomes.
Methods:
A quantitative real-time polymerase chain reaction was done on 40 BC patients who had undergone transurethral resection (TUR) or radical cystectomy and had a pathologically verified diagnosis of primary tumor without prior chemoradiotherapy as well as 20 patients with benign diseases who served as controls. The c-MET and HER2 expression levels were investigated, and their relationship with clinicopathological features was analyzed.
Results:
c-MET and HER2 gene expression were significantly higher, 6.1- and 4.5-fold, in the study group compared to the controls. The frequency of c-MET and HER2 overexpression in the study group was 80% (32/40) and 90% (36/40), respectively. c-MET overexpression was associated with pathological stage(P = 0.002), tumor grade (P = 0.019), muscle invasion (P = 0.008), and node involvement (P = 0.017), while HER2 overexpression was associated with pathological stage(P = 0.033), invasion to muscles (P = 0.003), and node involvement (P = 0.005). Based on the Log-rank test, patients expressing both c-MET and HER2 had the poorest disease-free survival rates among all studied patients (median = 10 m, 3.0-16.9 95%CI).
Conclusion:
There is a possible correlation between c-MET and HER2 gene overexpression and poor clinical outcomes in patients with BC.
