Quantitative Apparent Diffusion Coefficient Measurements Obtained by 3-Tesla MRI Are Correlated with Biomarkers of Bladder Cancer Proliferative Activity

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.

Intravoxel incoherent motion diffusion‐weighted imaging in assessing bladder cancer invasiveness and cell proliferation

“…[32][33][34] Ki-67 LI is an established marker of cell proliferation and tumor invasion, which can be a prognostic biomarker for bladder cancer that predicts clinical aggressiveness. [32][33][34][35] In this study, we found that the D and ADC values were negatively correlated with Ki-67 LI and that there were no significant correlations between the D* and f values and Ki-67 LI. This result confirmed that tumor invasion can be reflected by the extent of water molecular diffusion restriction rather than microvascular perfusion.…”

“…This finding is similar to other studies. 19,34,35 However, there were no significant correlations between D*, f value, and Ki-67 LI. As mentioned above, extracellular components such as blood flow velocity, vascular perfusion, or capillary volume contributed little to the aggressiveness of bladder tumors.…”

Update on multiparametric MRI of urinary bladder cancer

“…Known distinct genetic pathways between MIBC and non‐MIBC may often account for the differences in clinical outcomes and patient prognosis . Non‐MIBC are associated with mutations involving fibrobastic growth factors, which affects the kinase signaling pathways, while MIBC can be associated with defects in p53 and retinoblastoma tumor suppressor pathways, which affect cell cycle control . Knowledge of these pathways may be helpful for the discovery of useful radiomic features associated with different genetic mutations .…”

“…26,99 Non-MIBC are associated with mutations involving fibrobastic growth factors, which affects the kinase signaling pathways, while MIBC can be associated with defects in p53 and retinoblastoma tumor suppressor pathways, which affect cell cycle control. 99,100 Knowledge of these pathways may be helpful for the discovery of useful radiomic features associated with different genetic mutations. 38,100 A study by Sevcenco et al showed an association between ADC values and cell cycle regulators including p53 and p21.…”

“…99,100 Knowledge of these pathways may be helpful for the discovery of useful radiomic features associated with different genetic mutations. 38,100 A study by Sevcenco et al showed an association between ADC values and cell cycle regulators including p53 and p21. 100 Also Ki-67, which is a known marker for cellular proliferation, has been shown to inversely correlate with ADC values.…”