Combining tissue biomarkers with mpMRI to diagnose clinically significant prostate cancer. Analysis of 21 biomarkers in the PICTURE study

Abstract

BACKGROUND: Serum PSA and digital rectal examination remain the key diagnostic tools for detecting prostate cancer. However, due to the limited specificity of serum PSA, the applicability of this marker continues to be controversial. Recent use of image-guided biopsy along with pathological assessment and the use of biomarkers has dramatically improved the diagnosis of clinically significant cancer. Despite the two modalities working together for diagnosis biomarker research often fails to correlate findings with imaging. METHODS AND RESULTS: We looked at 21 prostate cancer biomarkers correlating our results with mpMRI data to investigate the hypothesis that biomarkers along with mpMRI data make a powerful tool to detect clinically significant prostate cancer. Biomarkers were selected based on the existing literature. Using a tissue microarray comprised of samples from the PICTURE study, with biopsies at 5 mm intervals and mpMRI data we analysed which biomarkers could differentiate benign and malignant tissue. Biomarker data were also correlated with pathological grading, mpMRI, serum PSA, age and family history. AGR2, CD10 and EGR protein expression was significantly different in both matched malignant and benign tissues. AMACR, ANPEP, GDF15, MSMB, PSMA, PTEN, TBL1XR1, TP63, VPS13A and VPS28 showed significantly different expression between Gleason grades in malignant tissue. The majority of the biomarkers tested did not correlate with mpMRI data. However, CD10, KHDRBS3, PCLAF, PSMA, SIK2 and GDF15 were differentially expressed with prostate cancer progression. AMACR and PTEN were identified in both pathological and image data evaluation. CONCLUSIONS: There is a high demand to develop biomarkers that would help the diagnosis and prognosis of prostate cancer. Tissue biomarkers are of particular interest since immunohistochemistry remains a cheap, reliable method that is widely available in pathology departments. These results demonstrate that testing biomarkers in a cohort consistent with the current diagnostic pathway is crucial to identifying biomarker with potential clinical utility.