Expression of ERG, an Ets Family Transcription Factor, Distinguishes Cutaneous Angiosarcoma from Histologic Mimics
Kristopher M McKay, Leona A Doyle, Alexander J Lazar, Jason L Hornick. The University of Texas M.D. Anderson Cancer Center, Houston, TX; Brigham and Women's Hospital & Harvard Medical School, Boston, MA
Background: Cutaneous angiosarcoma (AS) is most common on the scalp and face of elderly adults. The diagnosis of vasoformative AS is generally straightforward, whereas poorly differentiated AS can be difficult to distinguish from other neoplasms that arise in sun-damaged skin, such as squamous cell carcinoma (SCC), melanoma (MM), atypical fibroxanthoma (AFX), and leiomyosarcoma (LMS). A recent study showed that ERG, an Ets family transcription factor, is a sensitive and specific marker for endothelial differentiation. However, ERG expression has not been evaluated in non-AS cutaneous tumors. The purpose of this study was (1) to determine if immunohistochemistry (IHC) for ERG can distinguish cutaneous AS from histologic mimics and (2) to compare expression of ERG with FLI1, another Ets transcription factor widely expressed in vascular lesions.
Design: In total, 71 cutaneous head and neck tumors were retrieved from surgical files, including 22 AS (7 spindle cell, 4 epithelioid), 15 poorly differentiated SCC (5 spindle cell), 17 MM (8 spindle cell, 1 pseudovascular), 12 AFX (6 spindle cell, 6 pleomorphic), and 5 LMS. IHC was performed following antigen retrieval using a rabbit anti-ERG monoclonal antibody (1:2000; EPR3864(2); Epitomics) and a mouse anti-FLI1 monoclonal antibody (1:100; G146-222; BD Biosciences). The extent of immunoreactivity was graded according to the percentage of positive tumor cell nuclei (0, no staining; 1+, <5%; 2+, 5% to 25%; 3+, 26% to 50%; 4+, 51% to 75%; 5+, 76% to 100%), and the intensity was graded as weak, moderate, or strong.
Results: Distinct nuclear staining for ERG was observed in all 22 AS cases (95% strong 5+). All other tumor types were negative for ERG. FLI1 showed strong, diffuse nuclear staining in all AS cases. However, FLI1 was also positive in 13 of 15 (87%) SCC (40% moderate or strong; all 4-5+), 10 of 17 (59%) MM (12% moderate; variable extent), 11 of 12 (92%) AFX (25% moderate; variable extent), and 1 of 5 (20%) LMS (strong 5+). The sensitivity and specificity of ERG for AS are both 100%. The sensitivity of FLI1 for AS is also 100%, but the specificity is only 29%; if only moderate-strong staining is considered positive, the specificity is 76%.
Conclusions: ERG is a highly sensitive and specific marker for cutaneous AS and typically shows strong, diffuse nuclear staining. FLI1 is also highly sensitive for AS, but shows limited specificity. IHC for ERG is useful to support the diagnosis of AS, particularly in poorly differentiated cases.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 90, Tuesday Morning