Application of a Clinical Whole-Transcriptome Assay for Staging and Prognosis of Prostate Cancer Diagnosed in Needle Core Biopsy Specimens

Abstract

Molecular and genomic analysis of microscopic quantities of tumor from formalin-fixed, paraffin-embedded biopsy specimens has many unique challenges. Herein, we evaluated the feasibility of obtaining transcriptome-wide RNA expression to measure prognostic classifiers in diagnostic prostate needle core biopsy specimens. One-hundred fifty-eight samples from diagnostic needle core biopsy specimens (BX) and radical prostatectomies (RPs) were collected from 33 patients at three hospitals; each patient provided up to six tumor and benign samples. Genome-wide transcriptomic profiles were generated using Affymetrix Human Exon arrays for comparison of gene expression alterations and prognostic signatures between the BX and RP samples. A sufficient amount of RNA (>100 ng) was obtained from all RP specimens (n Z 77) and from 72 of 81 of BX specimens. Of transcriptomic features detected in RP, 95% were detectable in BX tissues and demonstrated a high correlation (r Z 0.96). Likewise, an expression signature pattern validated on RPs (Decipher prognostic test) showed correlation between BX and RP (r Z 0.70). Of matched BX and RP pairs, 25% showed discordant molecular subtypes. Genome-wide exon arrays yielded data of comparable quality from biopsy and RP tissues. The high concordance of tumor-associated gene expression changes between BX and RP samples provides evidence for the adequate performance of the assay platform with samples from prostate needle biopsy specimens with limited tumor volume. (J Mol Diagn 2016, 18: 395e406; http://dx

Tissue-based biomarkers in prostate cancer

“…When the evaluation was limited to the GC score, correlation between biopsy and RP specimens remained relatively high (r=0.70) with approximately 25% of matched biopsy and prostatectomy pairs demonstrating discordant molecular subtyping. [45] Similarly high rates of concordance (86%) are also reported by Lee et al[46]…”

“…[45] GPS was therefore evaluated for its predictive value in normal-appearing prostate tissue adjacent to prostate cancer in RP specimens. [120] When evaluated for development of clinical recurrence, the normal tissue with GPS score was shockingly significantly associated with a HR/20 units of 1.25 (95% CI 1.01-1.56, p = 0.024) as compared to the tumor (HR/20units was 3.42;95% CI 2.33-5.63; P < 0.001).…”

Biomarkers for Prostate Biopsy and Risk Stratification of Patients with Newly Diagnosed Prostate Cancer

“…63 Finally, Decipher is a panel of 22 RNA expression markers, previously shown to predict metastasis after prostatectomy and which can also be measured in biopsy specimens. 64 All of these tests are commercially available to assist in the initial treatment selection, although they are expensive and data on long-term comparative effectiveness are currently lacking.…”

How Precisely Can Prostate Cancer Be Managed?

“…Although biopsies yield a limited amount of tissue, the transcriptomic features detected in biopsy and prostatectomy tissues are highly correlated (r=0.96) [59]. The concordance between Decipher scores in prostatectomy tissue and biopsy tissue was reported to be as high as 86% in a recent study.…”