Nuclear hTERT Immunohistochemical Expression is Associated with Survival of Patients with Urothelial Bladder Cancer

Abstract

Background: The role of telomere in tumorigenesis is complex. While telomerase activation is suggested to be necessary for tumor growth, it may also help in diminishing genetic instability. The expressions of the telomerase reverse transcriptase/hTERT and the telomerase associated protein-1/hTEP-1 were investigated in relation to clinicopathological parameters and various proliferative and apoptotic biological markers. Materials and Methods: The immunohistochemical method ABC/HRP was performed on paraffin sections of 132 patients with urothelial bladder carcinomas to detect the proteins hTERT, hTEP-1, Ki-67, bcl-2, p53 and caspase-3. Results: The hTEP-1 protein was localized in the cytoplasm of cancerous cells (56.6%), while the hTERT protein was detected in the nuclei and the cytoplasm of cancerous cells (57.6% and 45.5%, respectively). hTEP-1 demonstrated an association with lower stage of the disease (p=0.036), as well as both nuclear and cytoplasmic hTERT (p=0.018 and p=0.0001, respectively). Cytoplasmic hTERT showed inverse correlation with the mutant p53 protein (p=0.047), while both cytoplasmic hTERT and hTEP-1 demonstrated parallel correlation with caspase-3 (p=0.004 and p=0.048, respectively). Nuclear hTERT associated with improved overall survival in multivariate analysis (p=0.007). Conclusion: The association of the hTERT protein with low stage urothelial carcinomas and improved patients' survival is in keeping with the idea that the early activation of telomerase may protect against genetic instability and the prevalence of aggressive malignant clones.