%0 Journal Article
%T Immunohistochemical Evaluation of Cell Cycle Regulators: Impact on Predicting Prognosis in Stage T1 Urinary Bladder Cancer
%A Hans Olsson
%A Per Hultman
%A Nastaran Monsef
%A Johan Rosell
%A Staffan Jahnson
%J ISRN Urology
%D 2012
%R 10.5402/2012/379081
%X Background and Objective. The cell cycle is regulated by proteins at different checkpoints, and dysregulation of this cycle plays a role in carcinogenesis. Matrix metalloproteinases (MMPs) are enzymes that degrade collagen and promote tumour infiltration. The aim of this study was to evaluate the expression of various cell cycle regulators and MMPs and to correlate such expression with progression and recurrence in patients with stage T1 urothelial carcinoma of the bladder (UCB). Patients and Methods. This population-based cohort study comprised 201 well-characterized patients with primary stage T1 urothelial carcinoma of the bladder. Immunohistochemistry was performed on formalin-fixed material to quantify expression of cell cycle regulators and two MMPs. Results. Normal expression of p53 and abnormal expression of MMP9 were associated with greater risk of tumour recurrence. Also, normal p16 expression was related to a lower risk of tumour progression. MMP2, p21, cyclin D1, and pRb showed no significant results that could estimate progression or recurrence. Conclusions. Normal p16 expression is associated with a lower risk of tumour progression, but immunohistochemistry on cell cycle regulators and MMPs has little value in predicting the prognosis in stage T1 UCB. 1. Introduction Prognostic factors in patients with superficial (stage Ta and T1) urothelial carcinoma of the bladder (UCB) have been the subject of several publications [1¨C6]. Depending on the patient and tumour characteristics, the probability of recurrence within one year after transurethral resection (TUR) ranges from approximately 15% to 70% [2], and the likelihood of progression within five years varies from about 7% to 40% [6]. UCB is a heterogeneous disease, and this is particularly apparent in stage T1. Clinical parameters and histopathological findings have only a limited capacity to predict the prognosis, although many studies have demonstrated that such prediction can be achieved by determining the presence of lymphovascular invasion (LVI), tumour grade, and T1 substage [7, 8]. The cell cycle is largely controlled by cell cycle regulators (proteins) at the Gap 1 S-phase and Gap 2 mitosis checkpoints. Dysregulation of the cell cycle at those mentioned steps may trigger carcinogenesis. Immunohistochemical analysis of different cell cycle regulators has helped to explain the molecular pathogenesis of UCB, and, to some extent, it has also had a prognostic impact [9¨C13]. Many interesting cell cycle regulators can be evaluated by immunohistochemistry (IHC) performed on paraffin-embedded
%U http://www.hindawi.com/journals/isrn.urology/2012/379081/