Abstract
PurposeTo investigate the association between Apparent Diffusion Coefficient (ADC) values and cell cycle and proliferative biomarkers (p53, p21, Ki67,) in order to establish its potential role as a noninvasive biomarker for prediction of cell cycle, proliferative activity and biological aggressiveness in bladder cancer.Materials and MethodsPatients with bladder cancer who underwent 3,0 Tesla DW-MRI of the bladder before TUR-B or radical cystectomy were eligible for this prospective IRB-approved study. Histological specimen were immunohistochemically stained for the following markers: p53, p21 and ki67. Two board-certified uropathologists reviewed the specimens blinded to DW-MRI results. Histological grade and T-stage were classified according to the WHO 2004 and the 2009 TNM classification, respectively. Nonparametric univariate and multivariate statistics including correlation, logistic regression and ROC analysis were applied.ResultsMuscle invasive bladder cancer was histologically confirmed in 10 out of 41 patients. All examined tissue biomarkers were significantly correlated with ADC values (p<0.05, respectively). Based on multivariate analysis, p53 and ADC are both independent prognostic factors for muscle invasiveness of bladder cancer (>/ = T2). (p = 0.013 and p = 0.018).ConclusionADC values are associated with cell cycle and proliferative biomarkers and do thereby reflect invasive and proliferative potential in bladder cancer. ADC and p53 are both independent prognostic factors for muscle invasiveness in bladder cancer.
Highlights
Bladder cancer is a malignant disease causing substantial morbidity and mortality
All examined tissue biomarkers were significantly correlated with Apparent Diffusion Coefficient (ADC) values (p,0.05, respectively)
ADC values are associated with cell cycle and proliferative biomarkers and do thereby reflect invasive and proliferative potential in bladder cancer
Summary
Bladder cancer is a malignant disease causing substantial morbidity and mortality. For optimized clinical management of patients with bladder cancer, an accurate prediction of the individual cancers biological behavior is needed. Standard prognostic factors such as pathological staging and grading are limited in this respect [1]. Molecular biomarkers taken from tissue specimen have become increasingly investigated in order to overcome these limitations and to accurately predict tumor grade and stage [2]. Previous studies based on cell cycle and tumor proliferation markers (p53, p21, ki67) have shown a prognostic role regarding patient outcome with muscle and non-muscle bladder cancer [1,2]. Computed tomography and magnetic resonance imaging (MRI) are regularly used for local staging of bladder cancer [3]
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