Heterogeneity of ERG expression in core needle biopsies of patients with early prostate cancer.
Prostate cancer is a heterogeneous, frequently multifocal disease with a broad spectrum of clinical, pathologic, and molecular characteristics. The TMPRSS2-ERG gene rearrangement is highly specific for prostate cancer. We used immunohistochemistry as a surrogate marker of the TMPRSS2-ERG fusion to study the heterogeneity of ERG expression in 280 prostate core needle biopsy series from 256 patients with early prostate cancer defined as 3 or less positive cores with no more than 50% of cancer per biopsy and a Gleason score of 7 or lower (3 + 4). Among the 163 patients with 2 or 3 cancer-positive biopsies, we found a subset of 19 patients (11.7%) with heterogeneous ERG expression. Thirteen (68.4%) of these patients showed biopsies with distinct positive and negative ERG staining in separate cores. The remaining 6 patients showed a mixture of both positive and negative staining within 1 biopsy core. This was either caused by different cancer foci (n = 3) or by one single, ERG-heterogeneous cancer focus (n = 3) in 1 core. Furthermore, we observed a heterogeneous ERG staining pattern over time in 6 (2.3%) of the 256 patients, in biopsies taken at various time points. An interobserver study of 21 cases with 2 separate cancer foci revealed that heterogeneity of ERG status in different cancer foci can be suspected based on morphologic differences (κ = 0.44). We conclude that heterogeneity of ERG expression is detectable in 10% to 15% of core biopsies of early prostate cancer. Further studies are needed to explore the clinical impact of heterogeneous ERG status in this patient group.
Institute for Pathology Liestal, Cantonal Hospital Baselland, CH-4410 Liestal, Switzerland. Electronic address: kirsten.mertz@ksbl.ch.
Kirsten D
KD
Mertz
Milo
M
Horcic
Seife
S
Hailemariam
Antonio
A
D'Antonio
Stephan
S
Dirnhofer
Arndt
A
Hartmann
Abbas
A
Agaimy
Serenella
S
Eppenberger-Castori
Ellen
E
Obermann
Gieri
G
Cathomas
Lukas
L
Bubendorf
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D062005:Biopsy, Large-Core Needle; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000378:metabolism*; D000071230:Transcriptional Regulator ERG
D014408:Biomarkers, Tumor; C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
Active surveillance; ERG; Heterogeneity; Immunohistochemistry; Prostate cancer