ERG Protein Expression in Human Tumors Detected With a Rabbit Monoclonal Antibody
ABSTRACT Avian v-ets erythroblastosis virus E26 oncogene homolog (ERG) is highly sensitive and specific for endothelial neoplasms and specific for prostate carcinoma. We characterized a rabbit anti-ERG antibody as an immunohistochemical agent to detect ERG expression in various tumors using tissue microarrays with a wide array of epithelial and mesenchymal tumors. ERG was positive in 63 (38%) of 168 prostate carcinomas and negative in all other epithelial tumors. ERG was positive in all 125 vascular lesions. It was also positive in the sarcomatoid component of a high-grade urothelial carcinoma and 6 (40%) of 15 meningiomas. Twelve (80%) of 15 meningiomas were positive for Fli1, including all 6 ERG-positive cases. Positive immunostaining with this antibody is therefore highly specific for prostate carcinoma and vascular lesions, with a few caveats. ERG is rarely detected in nonvascular mesenchymal tumors with this antibody. Furthermore, about 40% of meningiomas are also positive for ERG immunohistochemically, probably because of cross-reactivity with Fli1.
- SourceAvailable from: Cristina Magi-Galluzzi[Show abstract] [Hide abstract]
ABSTRACT: OBJECTIVES To evaluate how often ERG, a highly prostate-cancer-specific marker, is expressed in isolated high grade prostatic intraepithelial neoplasia (HGPIN) by immunohistochemistry. To study whether a positive ERG immunostain in HGPIN correlates with prostate cancer (PCa) detection in subsequent repeat biopsies. PATIENTS AND METHODS Patients with initial HGPIN in biopsies and at least one follow-up prostate biopsy were included. Biopsies with HGPIN were immunostained for ERG. The ERG staining results were then correlated with the PCa risk in subsequent biopsies. RESULTS The mean age of 94 patients was 63 years (range 48-78). A mean of 1.8 (range 1-5) repeat biopsy sessions were carried out at a mean interval of 27.4 months (range 1.5-140). The repeat biopsies showed PCa and non-cancer lesions (benign, HGPIN, atypical glands suspicious for cancer) in 36 patients (38%) and 58 patients (62%) respectively. ERG immunostain was positive in five (5.3%) biopsies with HGPIN, in which PCa was found in two (40%) subsequent biopsies. Of 89 biopsies with negative ERG staining, PCa was found in 34 (38%) repeat biopsies. The cancer detection rate was not different between ERG positive and negative cases (P = 0.299). CONCLUSIONS This is the first study to investigate the ERG protein expression in prostate biopsy containing HGPIN only and its use to stratify the cancer risk associated with HGPIN. We found that ERG expression is distinctly uncommon in isolated HGPIN (5.3%). Positive ERG expression is not associated with increased cancer detection in subsequent repeat biopsies. The use of ERG immunostain in the evaluation and cancer risk stratification of HGPIN is of limited value.BJU International 10/2012; 110(11B). DOI:10.1111/j.1464-410X.2012.11557.x
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ABSTRACT: Ewing family tumors (EFTs) and prostate carcinomas are characterized by rearrangement of ETS genes, most commonly FLI1 (EFTs) and ERG (prostate carcinomas). Previously, we characterized an antibody against ERG (EPR3864) for detecting ERG-rearranged prostate carcinoma. Because EPR3864 also cross-reacts with FLI1, we evaluated the usefulness of EPR3864 for discriminating EFTs from other small round blue cell tumors (SRBCTs) with immunohistochemistry. Of 57 evaluable EFTs, 47 (82%) demonstrated at least moderate, diffuse, nuclear ERG/FLI1 staining (including 89% and 100% of cases with confirmed EWSR1:FLI1 and EWSR1:ERG fusions, respectively), of which 1, 3, and 43 showed negative, cytoplasmic, or membranous CD99 staining, respectively. Among other SRBCTs (61 cases, 7 types), at least moderate, diffuse, nuclear EPR3864 staining was seen in all precursor B-lymphoblastic lymphomas/leukemias and subsets of Burkitt lymphomas (10%) and synovial sarcomas (45%). In summary, EPR3864 may be useful in detecting EWSR1:FLI1 and EWSR1:ERG rearranged EFTs in addition to prostate carcinomas.American Journal of Clinical Pathology 06/2013; 139(6):771-779. DOI:10.1309/AJCPN4L1BMRQPEIT
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ABSTRACT: Epithelioid sarcoma is a rare, aggressive keratin-positive sarcoma that co-expresses CD34 in 50% of cases and may mimic an angiosarcoma. Recently, we have observed one case of epithelioid sarcoma that labeled for ERG, an ETS family regulatory transcription factor, which is considered to be a reliable marker for vascular differentiation. We investigated the prevalence of nuclear expression of ERG and FLI1, a homologous transcription factor, in these tumors. A formalin-fixed paraffin-embedded tissue microarray of 37 epithelioid sarcomas was examined. Immunohistochemistry was performed using anti-ERG monoclonal antibody to the N-terminus, anti-ERG monoclonal antibody to the C-terminus and anti-FLI1 monoclonal antibody. Comparison was made with CD34, CD31, and D2-40 labeling. The extent of immunoreactivity was graded according to the percentage of positive tumor cell nuclei (0: no staining; 1+: <5%; 2+: 5-25%; 3+: 26-50%; 4+: 51-75%; and 5+: 76-100%), and the intensity of staining was graded as weak, moderate, or strong. Nuclear staining for the N-terminus of ERG was seen in 19 out of 28 cases: 10 with diffuse(4 to 5+) strong/moderate labeling; 1 with 2+ moderate labeling and 8 with weak labeling (1 to 4+, 2 each). Focal staining for the C-terminus of ERG was seen in only 1 out of 29 cases (2+ moderate). FLI1 labeling was seen in nearly all (28 out of 30) cases: 16 with diffuse (5+) predominantly moderate labeling, and 8 cases with diffuse(5+) weak labeling. The remainder had variable moderate (1 to 3+) or weak (1 to 4+) FLI1 staining. CD34 was positive in 22 out of 30 cases and D2-40 was found to be positive in 22 out of 31 cases. All cases were negative for CD31 (0 out of 30). Epithelioid sarcoma can label with antibodies to the N-terminus of ERG, FLI1, and D2-40, which may cause diagnostic confusion for a vascular tumor. A panel of other antibodies including SMARCB1 and CD31 should be used in evaluating these tumors. ERG antibody selection is also critical, as those directed against the C-terminus are less likely to label epithelioid sarcoma.Modern Pathology advance online publication, 27 September 2013; doi:10.1038/modpathol.2013.161.Modern Pathology 09/2013; DOI:10.1038/modpathol.2013.161