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Differential microRNA expression levels in TRUS biopsies with diverse histopathologies
Kai H. Hammerich, MD, PhD, John E. Humphrey, MD, Justin M. Zbrzezny, MD, Kelly Summerhayes, BS, Patrick A. Teebagy, BA, John A. Libertino, MD, Antonia H. Holway, PhD, Kimberly Rieger-Christ, PhD.
Lahey Clinic Medical Center, Burlington, MA, USA.
TBackground
Clinical decisions surrounding prostate cancer are based on the findings of Digital Rectal Exams (DREs), Prostate Specific Antigen (PSA) levels and histopathological analysis of Transrectal Ultrasound (TRUS) guided biopsies. However, molecular pathway analysis has traditionally been limited to prostatectomy specimens. The aim of this study was to evaluate microRNA expression levels associated with different histopathologies at the time of TRUS biopsy.
Methods
Total RNA was extracted from TRUS biopsies and pooled for microarray analysis. Seven subgroups were created representing benign tissue, atypia, Gleason Sum (GS) 6, 7, and ≥8 adenocarcinoma, and patients with negative or positive lymph nodes (LN) on prostatectomy. MiRNA expression was verified by qRT-PCR on individual specimens.
Results
MicroRNA profiling identified 142, 58 and 13 microRNAs that were differentially expressed in GS 6 versus 8, GS 6 versus 7 and LN positive versus LN negative comparisons, respectively. qRT-PCR of significantly expressed miRNAs on individual patient samples validated this differential expression. As an example, miRNA-143 expression differentiated benign from cancer while biopsies containing atypical glands varied with miRNA-143 levels consistent with both cancer and benign cores.
Conclusions
TRUS biopsy samples showed differential miRNA expression among cores with diverse histopathologies. Several of these changes have previously been reported in prostatectomy specimens, validating this approach. MiRNA-143 expression levels in TRUS biopsies may provide predictive information when histopathological analysis of the core tissue is inconclusive. Analysis of microRNA expression levels in TRUS specimens holds promise to improve diagnosis, prognosis, and characterization of prostate cancer.
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