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 biopsy and RP samples provides evidence for the adequate performance of the assay platform with samples from prostate needle biopsy specimens with limited tumor volume.
The Journal of molecular diagnostics : JMD. 2016 Mar 02 [Epub ahead of print]
Beatrice S Knudsen, Hyung L Kim, Nicholas Erho, Heesun Shin, Mohammed Alshalalfa, Lucia L C Lam, Imelda Tenggara, Karen Chadwich, Theo Van Der Kwast, Neil Fleshner, Elai Davicioni, Peter R Carroll, Matthew R Cooperberg, June M Chan, Jeffry P Simko
Departments of Biomedical Sciences and Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California., Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California., Research and Development, GenomeDx Biosciences, Inc., Vancouver, British Columbia, Canada., Research and Development, GenomeDx Biosciences, Inc., Vancouver, British Columbia, Canada., Research and Development, GenomeDx Biosciences, Inc., Vancouver, British Columbia, Canada., Research and Development, GenomeDx Biosciences, Inc., Vancouver, British Columbia, Canada., Department of Urology, University of California San Francisco, San Francisco, California., Department of Urology, University Health Network, Toronto, Ontario, Canada., Department of Pathology, Princess Margaret Cancer Center, Toronto, Ontario, Canada., Department of Urology, University Health Network, Toronto, Ontario, Canada., Research and Development, GenomeDx Biosciences, Inc., Vancouver, British Columbia, Canada. Department of Urology, University of California San Francisco, San Francisco, California., Department of Urology, University of California San Francisco, San Francisco, California; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California., Department of Urology, University of California San Francisco, San Francisco, California; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California., Department of Urology, University of California San Francisco, San Francisco, California; Department of Anatomic Pathology, University of California San Francisco, San Francisco, California.