title: 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 = 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 = 0.96). Likewise, an expression signature pattern validated on RPs (Decipher prognostic test) showed correlation between BX and RP (r = 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.
authors.affiliation: Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Beatrice S
authors.initials: BS
authors.lastname: Knudsen
authors.affiliation: Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Hyung L
authors.initials: HL
authors.lastname: Kim
authors.affiliation: Department of Research and Development, GenomeDx Biosciences, Inc., Vancouver, British Columbia, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Erho
authors.affiliation: Department of Research and Development, GenomeDx Biosciences, Inc., Vancouver, British Columbia, Canada.
authors.forename: Heesun
authors.initials: H
authors.lastname: Shin
authors.affiliation: Department of Research and Development, GenomeDx Biosciences, Inc., Vancouver, British Columbia, Canada.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alshalalfa
authors.affiliation: Department of Research and Development, GenomeDx Biosciences, Inc., Vancouver, British Columbia, Canada.
authors.forename: Lucia L C
authors.initials: LLC
authors.lastname: Lam
authors.affiliation: Department of Urology, University of California San Francisco, San Francisco, California.
authors.forename: Imelda
authors.initials: I
authors.lastname: Tenggara
authors.affiliation: Department of Urology, University Health Network, Toronto, Ontario, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Chadwich
authors.affiliation: Department of Pathology, Princess Margaret Cancer Center, Toronto, Ontario, Canada.
authors.forename: Theo
authors.initials: T
authors.lastname: Van Der Kwast
authors.affiliation: Department of Urology, University Health Network, Toronto, Ontario, Canada.
authors.forename: Neil
authors.initials: N
authors.lastname: Fleshner
authors.affiliation: Department of Research and Development, GenomeDx Biosciences, Inc., Vancouver, British Columbia, Canada. Electronic address: elai@genomedx.com.
authors.forename: Elai
authors.initials: E
authors.lastname: Davicioni
authors.affiliation: Department of Urology, University of California San Francisco, San Francisco, California.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Carroll
authors.affiliation: Department of Urology, University of California San Francisco, San Francisco, California; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Cooperberg
authors.affiliation: Department of Urology, University of California San Francisco, San Francisco, California; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: June M
authors.initials: JM
authors.lastname: Chan
authors.affiliation: Department of Urology, University of California San Francisco, San Francisco, California; Department of Anatomic Pathology, University of California San Francisco, San Francisco, California.
authors.forename: Jeffry P
authors.initials: JP
authors.lastname: Simko
mesh_terms: D062005:Biopsy, Large-Core Needle; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D059467:Transcriptome