Prognostic Value of Bcl-2 and Bax Tumor Cell Expression in Patients with Non Muscle-Invasive Bladder Cancer Receiving Bacillus Calmette-Guerin Immunotherapy

Abstract

Apoptosis is the distinctive form of programmed cell death that complements cell proliferation in maintaining normal tissue homeostasis. The significance of constitutive apoptosis in the recurrence of Non Muscle Invasive Bladder Cancer has yet to be investigated. The aim of this study is to investigate the prognostic significance of Bax and Bcl-2 in terms of recurrence after BCG immunotherapy. Immunohistochemical analysis was performed on frozen biopsies to evaluate bcl-2 and Bax proteins expression in 28 cases of NMIBC. All patients with confirmed NMIBC were treated with intravesical BCG-immunotherapy. The follow up was performed for 26 months. The correlation between clinicopathological, immunohistochemical data and the response to BCG therapy was performed. Univariate analysis showed that, PT1 stage, High grade and Bax expression increased significantly the risk of recurrence (P = 0.015, P = 0.015 and P= 0.034 respectively). In addition, multivariate analysis selected the model involving stage, age, Bax and Bcl-2 expression as the best independent variables of recurrence. In conclusion, the expression of Bcl-2 and Bax in NMIBC could have a prognostic value in assessing the risk of recurrence after BCG immunotherapy. These findings require further investigations on larger cohort in order to ascertain new molecular markers of the response to BCG immunotherapy.

Developing proteomic biomarkers for bladder cancer: towards clinical application

“…96 Numerous studies have investigated levels of selected proteins in archival collections of tissue samples. Among these were apoptosis regulatory proteins Bcl-2 and Bax, 99 inhibitors of apoptosis such as survivin 97 , proliferation associated proteins such as TP53, cyclin-dependent kin ase inhibitor 1 (also known as p21), cyclin-dependent kinase inhibitor 1B (also known as p27), retinoblastomaassociated protein, 100 galectin-8, 101 serpin B5, 102 cyclin D1, 103 double-strand break repair protein MRE11A, DNA repair protein RAD50, Nibrin, serine-protein kinase ATM, histone H2AX, 104 PLK1, 97 carbonic anhydrase 9 105 and prostaglandin G/H synthase 2. 106 These proteins were assessed either as prognostic markers or for prediction of the outcomes of radiotherapy and/or chemotherapy in patients with bladder cancer ( Table 4).…”

Pioglitazone Use and Risk of Bladder Cancer: an In Vitro Study

“…The inhibition of bladder cell growth by PIO might be explained by cell cycle arrest, the induction of apoptosis, and/or terminal differentiation 36 . It was proposed that thiazolidinediones, PPARγ ligands, could induce tumor cell apoptosis by downregulating Bcl-2 and upregulating Bax 37 - 38 .…”

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