Editor's Commentary - Characterization of bone metastases from rapid autopsies of prostate cancer patients

BERKELEY, CA (UroToday.com) - In Clinical Cancer Research, Dr. Rohit Mehra and colleagues performed gene expression profiling of bone metastasis from recently deceased prostate cancer (CaP) patients for subsequent characterization.

This is important because fresh metastatic tissue is difficult to obtain, and “warm-autopsy” programs permit the rapid acquisition of tissue. “Warm-autopsy” refers to an interval of <3 hours between patient death and post-mortem examination. The goal of the report is to highlight techniques associated with this unique basic and translational endeavor.

Using bone scans for guidance, bone marrow from metastatic sites was procured for RNA extraction and phenotypic assessment. Long bones were sectioned in a sagital rather than cross-sectional manner, permitting non-ossified metastatic sites to be found. PCR was performed using primers for genes associated with CaP such as AMACR, ERG, LKL3, PCA3, and TMPRSS2:ERG. Gene expression was compared between the soft bone metastatic tissues and matched non-osseous metastatic samples. Array CGH analysis was performed on matched pairs of tissues. Gene expression analysis was also performed in 5 sets of matched samples.

They found bone marrow to be variably present in osseous metastatic sites. Tumor was found in both the marrow cavity and periosteal location. Marrow cavity sites had a much higher tumor density compared with hard bone. PCA3 and PSA had high levels of expression while ERG, AMACR, and TMPRSS2-ERG were variable. In the CGH analysis, 194 copy gains and 118 copy losses were identified. Ultimately, they were unable to identify any regions of interest in the CGH analysis. In the gene expression analysis, a global metastasis gene signature was not differentially expressed between non-osseous and osseous sites. Bone morphogenetic proteins had greater expression in osseous tissue. One gene, Dicer1 that encodes a protein that functions as a ribonuclease and is required by the RNA interference to produce active small RNA that represses gene expression was downregulated. This may be important regarding microRNAs.

Mehra R, Kumar-Sinha C, Lonigro RJ, Shankar S, Jing X, Phillips NE, Han B, Cao X, Smith DC, Shah RB, Chinnaiyan AM, Pienta KJ


Clin Cancer Res. 2011 Jun 15;17(12):3924-32

PubMed Abstract
PMID: 21555375

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