ERG protein expression over time: from diagnostic biopsies to radical prostatectomy specimens in clinically localised prostate cancer

TY - JOUR

T1 - ERG protein expression over time

T2 - from diagnostic biopsies to radical prostatectomy specimens in clinically localised prostate cancer

AU - Berg, Kasper Drimer

AU - Brasso, Klaus

AU - Thomsen, Frederik Birkebæk

AU - Røder, M Andreas

AU - Holten-Rossing, Henrik

AU - Toft, Birgitte Grønkær

AU - Iversen, Peter

AU - Vainer, Ben

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PY - 2015/10/1

Y1 - 2015/10/1

N2 - Aims We evaluated the consistency in ERG protein expression from diagnostic specimens through rebiopsies to radical prostatectomies in patients with clinically localised prostate cancer to investigate the validity of ERG status in biopsies. Methods ERG expression was assessed by immunohistochemistry (IHC) in 625 biopsy sets and 86 radical prostatectomy specimens from 265 patients with prostate cancer managed on active surveillance. For IHC, a rabbit monoclonal primary antibody was used (clone: EPR3864). TMPRSS2-ERG fluorescence in situ hybridisation (FISH) analyses were performed in 74 biopsies using the FISH ZytoLight TriCheck Probe (SPEC ERG/TMPRSS2). FISH results were correlated with IHC findings. Results The concordance between FISH and IHC was 97.3% and IHC demonstrated a sensitivity and specificity for ERG rearrangement of 100% and 95.5%, respectively. Applying IHC, 38.1% of patients were ERGpositive, 53.6% were ERG-negative and 8.3% showed both ERG-positive and negative tumour foci (ERG heterogeneous) at diagnosis. When ERG status was dichotomised (ERG-positive or heterogeneous vs ERGnegative), 95.6%-97.1% of patients did not experience ERG reclassification during the first two rounds of rebiopsies. The concordance in ERG status between biopsies and surgical specimen was 89.5%-94.2% depending on the number of rebiopsies included. Sampling bias was assumed to explain most (81.3%) of the mismatches in ERG status. Conclusions Consistency in ERG status ranged from 90% to 95% for patients undergoing serial biopsies and radical prostatectomy. This indicates that biopsies can be used reliably to investigate ERG's prognostic and predictive value.

AB - Aims We evaluated the consistency in ERG protein expression from diagnostic specimens through rebiopsies to radical prostatectomies in patients with clinically localised prostate cancer to investigate the validity of ERG status in biopsies. Methods ERG expression was assessed by immunohistochemistry (IHC) in 625 biopsy sets and 86 radical prostatectomy specimens from 265 patients with prostate cancer managed on active surveillance. For IHC, a rabbit monoclonal primary antibody was used (clone: EPR3864). TMPRSS2-ERG fluorescence in situ hybridisation (FISH) analyses were performed in 74 biopsies using the FISH ZytoLight TriCheck Probe (SPEC ERG/TMPRSS2). FISH results were correlated with IHC findings. Results The concordance between FISH and IHC was 97.3% and IHC demonstrated a sensitivity and specificity for ERG rearrangement of 100% and 95.5%, respectively. Applying IHC, 38.1% of patients were ERGpositive, 53.6% were ERG-negative and 8.3% showed both ERG-positive and negative tumour foci (ERG heterogeneous) at diagnosis. When ERG status was dichotomised (ERG-positive or heterogeneous vs ERGnegative), 95.6%-97.1% of patients did not experience ERG reclassification during the first two rounds of rebiopsies. The concordance in ERG status between biopsies and surgical specimen was 89.5%-94.2% depending on the number of rebiopsies included. Sampling bias was assumed to explain most (81.3%) of the mismatches in ERG status. Conclusions Consistency in ERG status ranged from 90% to 95% for patients undergoing serial biopsies and radical prostatectomy. This indicates that biopsies can be used reliably to investigate ERG's prognostic and predictive value.

KW - Aged

KW - Biomarkers, Tumor

KW - Biopsy

KW - Humans

KW - Immunohistochemistry

KW - In Situ Hybridization, Fluorescence

KW - Male

KW - Middle Aged

KW - Predictive Value of Tests

KW - Prospective Studies

KW - Prostatectomy

KW - Prostatic Neoplasms

KW - Reproducibility of Results

KW - Time Factors

KW - Trans-Activators

U2 - 10.1136/jclinpath-2015-202894

DO - 10.1136/jclinpath-2015-202894

M3 - Journal article

C2 - 26060265

SN - 0021-9746

VL - 68

SP - 788

EP - 794

JO - Journal of Clinical Pathology

JF - Journal of Clinical Pathology

IS - 10

ER -