Quantitative Multiparametric MRI Features and PTEN Expression of Peripheral Zone Prostate Cancer: A Pilot Study.

OBJECTIVE The objective of our study was to investigate associations between quantitative image features of multiparametric MRI of the prostate and PTEN expression of peripheral zone prostate cancer. MATERIALS AND METHODS A total of 45 peripheral zone cancer foci from 30 patients who had undergone multiparametric prostate MRI before prostatectomy were identified by a genitourinary pathologist and a radiologist who reviewed histologic findings and MR images. Histologic sections of cancer foci underwent immunohistochemical analysis and were scored according to the percentage of tumor-positive cells expressing PTEN as negative (0-20%), mixed (20-80%), or positive (80-100%). Average and 10th percentile apparent diffusion coefficient (ADC) values, skewness of T2-weighted signal intensity histogram, and quantitative perfusion parameters (i.e., forward volume transfer constant [K(trans)], extravascular extracellular volume fraction [ve], and reverse reflux rate constant between the extracellular space and plasma [k(ep)]) from the Tofts model were calculated for each cancer focus. Associations between the quantitative image features and PTEN expression were analyzed with the Spearman rank correlation coefficient (r). RESULTS Analysis of the 45 cancer foci revealed that 21 (47%) were PTEN-positive, 12 (27%) were PTEN-negative, and 12 (27%) were mixed. There was a weak but significant negative correlation between Gleason score and PTEN expression (r = -0.30, p = 0.04) and between k(ep) and PTEN expression (r = -0.35, p = 0.02). There was no significant correlation between other multiparametric MRI features and PTEN expression. CONCLUSION This preliminary study of radiogenomics of peripheral zone prostate cancer revealed weak-but significant-associations between the quantitative dynamic contrast-enhanced MRI feature k(ep) and Gleason score with PTEN expression. These findings warrant further investigation and validation with the aim of using multiparametric MRI to improve risk assessment of patients with prostate cancer.

[1]  Linda M. Johnson,et al.  Defining the radiobiology of prostate cancer progression: An important question in translational prostate cancer research , 2014, Experimental biology and medicine.

[2]  Aytekin Oto,et al.  Apparent diffusion coefficient for prostate cancer imaging: impact of B values. , 2014, AJR. American journal of roentgenology.

[3]  T. Kwast Prognostic prostate tissue biomarkers of potential clinical use , 2014, Virchows Archiv.

[4]  H. Hricak,et al.  Radiogenomics of clear cell renal cell carcinoma: associations between CT imaging features and mutations. , 2013, Radiology.

[5]  Thomas Hambrock,et al.  Assessment of prostate cancer aggressiveness using dynamic contrast-enhanced magnetic resonance imaging at 3 T. , 2013, European urology.

[6]  Fang-Ming Deng,et al.  Prostate cancer: comparison of dynamic contrast-enhanced MRI techniques for localization of peripheral zone tumor. , 2013, AJR. American journal of roentgenology.

[7]  J. Lindberg,et al.  Genetic markers associated with early cancer‐specific mortality following prostatectomy , 2013, Cancer.

[8]  M. Giger,et al.  Quantitative analysis of multiparametric prostate MR images: differentiation between prostate cancer and normal tissue and correlation with Gleason score--a computer-aided diagnosis development study. , 2013, Radiology.

[9]  J. Cuzick,et al.  Prognostic value of PTEN loss in men with conservatively managed localised prostate cancer , 2013, British Journal of Cancer.

[10]  G. Bubley,et al.  Clonal progression of prostate cancers from Gleason grade 3 to grade 4. , 2013, Cancer research.

[11]  M. Rubin,et al.  Novel Dual Color Immunohistochemical methods for detecting ERG-PTEN and ERG-SPINK1 status in prostate carcinoma , 2013, Modern Pathology.

[12]  J. Oh,et al.  Prostate‐specific antigen vs prostate‐specific antigen density as a predictor of upgrading in men diagnosed with Gleason 6 prostate cancer by contemporary multicore prostate biopsy , 2012, BJU international.

[13]  D. D. Maki,et al.  Radiogenomic analysis of breast cancer using MRI: a preliminary study to define the landscape. , 2012, AJR. American journal of roentgenology.

[14]  Olivier Gevaert,et al.  Non-small cell lung cancer: identifying prognostic imaging biomarkers by leveraging public gene expression microarray data--methods and preliminary results. , 2012, Radiology.

[15]  M. Roobol,et al.  Defining and predicting indolent and low risk prostate cancer. , 2012, Critical reviews in oncology/hematology.

[16]  Hideaki Mizuno,et al.  Molecular classification of prostate cancer using curated expression signatures , 2011, Proceedings of the National Academy of Sciences.

[17]  Ferenc A. Jolesz,et al.  Radiogenomic Mapping of Edema/Cellular Invasion MRI-Phenotypes in Glioblastoma Multiforme , 2011, PloS one.

[18]  Jianfeng Xu,et al.  PTEN Protein Loss by Immunostaining: Analytic Validation and Prognostic Indicator for a High Risk Surgical Cohort of Prostate Cancer Patients , 2011, Clinical Cancer Research.

[19]  Devkumar Mustafi,et al.  Use of a reference tissue and blood vessel to measure the arterial input function in DCEMRI , 2010, Magnetic resonance in medicine.

[20]  C. Sander,et al.  Integrative genomic profiling of human prostate cancer. , 2010, Cancer cell.

[21]  Alexandre Mamedov,et al.  Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  B. G. Blijenberg,et al.  Screening and prostate-cancer mortality in a randomized European study. , 2009, The New England journal of medicine.

[23]  J. Squire,et al.  FISH analysis of 107 prostate cancers shows that PTEN genomic deletion is associated with poor clinical outcome , 2007, British Journal of Cancer.

[24]  William R Sellers,et al.  The biology and clinical relevance of the PTEN tumor suppressor pathway. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  Milica Medved,et al.  Semiquantitative analysis of dynamic contrast enhanced MRI in cancer patients: Variability and changes in tumor tissue over time , 2004, Journal of magnetic resonance imaging : JMRI.

[26]  M. Knopp,et al.  Estimating kinetic parameters from dynamic contrast‐enhanced t1‐weighted MRI of a diffusable tracer: Standardized quantities and symbols , 1999, Journal of magnetic resonance imaging : JMRI.

[27]  M. Wigler,et al.  PTEN, a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer , 1997, Science.