Operator dependent choice of prostate cancer biopsy has limited impact on a gene signature analysis for the highly expressed genes IGFBP3 and F3 in prostate cancer epithelial cells.
Author(s): Peng Z, Andersson K, Lindholm J, Bodin I, Pramana S, Pawitan Y, Nistér M, Nilsson S, Li C
Publication: PLoS One, 2014, Vol. 9, Page e109610
PubMed ID: 25296164 PubMed Review Paper? No
Purpose of Paper
This paper compared transcript levels of insulin-like growth factor-binding protein 3 (IGFBP3), factor III (F3) and vestigial like family member 3 (VGLL3) between case-matched tumor biopsies as well as case-matched tumor and benign specimens procured from prostate tissue.
Conclusion of Paper
Differences in cycle threshold (CT) values for IGFBP3, F3 and VGLL3 between case-matched cancer biopsies was less than2 CTs for 79%, 74% and 46.5% of cases, respectively (34, 32 and 29 of 43 cases out of x cases, respectively). Mean differences in F3 and VGLL3 CT values between matched tumor and benign specimens were generally larger than those between tumor biopsies, but the range of differences was comparable. In contrast, the mean difference in IGFBP3 CT values between case-matched tumor and benign specimens was comparable to that observed among case-matched tumor biopsies. Further investigation of cases with the largest differences between case-matched tumor biopsies revealed that the majority could be attributed to specimens that had less than 0.1mm3 tissue, contained greater than 30% stromal cells, or contained infiltrative/invasive cancer surrounded by stromal cells.
Studies
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Study Purpose
The purpose of this study was to compare transcript levels of IGFBP3, F3 and VGLL3 between case-matched tumor biopsies and case-matched tumor and benign specimens procured from prostate tissue. FFPE biopsies from 43 patients with prostate cancer were obtained over a 6 year period. The first section (5 µM) was H&E stained and used to define tumor areas. Tumor areas of at least 10 mm2 from unstained 10 µM sections were scraped into microcentrifuge tubes and RNA was extracted using the HighPure FFPE RNA Micro Kit. Two tumor biopsy specimens were available for 33 cases, and 3-4 tumor biopsy specimens were available for the remaining 10 cases. For 30 cases a benign specimen was also available. Transcript levels of IGFBP3, F3, VGLL3 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were determined in biopsies with the highest Gleason scores by multiplex real-time RT-PCR.
Summary of Findings:
Although 79.4% of tumor biopsy specimens contained >90% cancer epithelial cells, a few specimens had up to 40% stromal cells. The difference in CT values for IGFBP3, F3 and VGLL3 between matched biopsies was less than2 CTs for 79%, 74% and 46.5% of cases, respectively (34, 32 and 29, out of 43cases respectively). VGLL3 levels differed by 2-4 CTs in 32.5% of cases (14 of 43 cases). Mean differences in F3 and VGLL3 CT values between case-matched tumor and benign specimens were generally larger than those between case-matched tumor biopsies, but the range of differences was comparable. In contrast, the mean difference in IGFBP3 CT values between case-matched tumor and benign specimens was comparable to that observed among case-matched tumor biopsies. Further investigation of cases with the largest differences between case-matched tumor biopsies revealed that the majority could be attributed to specimens that had less than 0.1mm3 tissue, contained greater than 30% stromal cells, or contained infiltrative/invasive cancer surrounded by stromal cells.
Biospecimens
Preservative Types
- Formalin
Diagnoses:
- Neoplastic - Benign
- Neoplastic - Carcinoma
Platform:
Analyte Technology Platform RNA Real-time qRT-PCR Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Biospecimen Aliquots and Components Biospecimen heterogeneity Intratumoral sampling (exact positions not specified)
Real-time qRT-PCR Specific Targeted nucleic acid IGFBP3
F3
VGLL3
Biospecimen Aliquots and Components Biospecimen components Benign
Neoplastic