Angiosarcoma and atypical vascular lesions of the breast: diagnostic and prognostic role of MYC gene amplification and protein expression

Abstract

MYC amplification has been reported as a prominent feature of secondary angiosarcomas (SAS). The differential diagnosis between atypical vascular lesion (AVL) and low-grade angiosarcoma (AS) can be occasionally very difficult or even impossible, and MYC amplification status has been pointed as an important diagnostic tool to distinguish cutaneous vascular lesions of the breast. We assessed MYC amplification and protein expression status by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC), respectively, in 49 patients diagnosed with breast AS, and 30 patients diagnosed with post-radiation AVL of the breast. Clinical and pathological features, and follow-up data were collected, and survival analyses were performed. Among 37 patients with SAS, twenty patients had tumors with high-level MYC amplification and protein overexpression (54 %). None of primary angiosarcomas (PAS) or AVL cases showed MYC amplification or protein expression. Concordance between MYC amplification (FISH) and protein expression (IHC) was 100 % in AVL, PAS, and SAS. Survival analysis of the SAS patients demonstrates that those with MYC amplification had a significantly worse overall survival compared to cases without MYC amplification (P = 0.035). There was a non-significant trend toward a poor disease-free survival between cases with and without MYC amplification (P = 0.155). Our findings show that MYC amplification is a highly specific but poorly sensitive marker for SAS and, therefore, a negative result does not exclude the diagnosis of angiosarcoma. MYC amplification was associated with adverse prognosis, suggesting a prognostic role of MYC amplification status on SAS of the breast.

Radiotherapy-Associated Long-term Modification of Expression of the Inflammatory Biomarker Genes ARG1, BCL2L1, and MYC

“…Finally, MYC is a well-known transcription factor that plays a central role in cancer development processes including cell proliferation, growth, and apoptosis. MYC has been previously upregulated in cases of radiation-induced angiosarcoma (40, 41) and glioblastoma, with its expression associated with longer overall survival (42) but here we see a strong and consistent downregulation in all endometrial cancer patients after radiotherapy.…”

Clinical outcomes in breast angiosarcoma patients: A rare tumor with unique challenges

“…Sorafenib, a multi‐targeted tyrosine kinase inhibitor of RAF, VEGF 1‐3, PDGFRβ, FLT‐3, RET, and c‐KIT, was studied by the SWOG intergroup in a phase II (S0505) trial in advanced soft tissue sarcoma: no confirmed response was observed in the 37 patients, and the study was closed prematurely . Amplification of MYC is a feature of RAAS seen in 54% of cases . MYC amplification can be assessed by FISH or immunohistochemistry, which can aid in differentiating RAAS from the benign entity of atypical vascular lesion where MYC is not overexpressed.…”

Post‐radiation vascular lesions of the breast

“…These studies indicate that MYC protein expression in AS appears to be helpful in the differential diagnosis of AVL and AS in the breast but not in other sites. Also, it appears that MYC is not entirely specific for secondary AS, as was originally suggested; because a rare subset of primary AS (UV‐related) may also show MYC amplification.…”

“…Such ancillary studies may be of aid in some cases for arriving at the correct diagnosis, particularly on limited biopsies or if the biopsy is taken from the periphery of the lesion. However, it is important to note that MYC amplification is not detected in all cases of secondary AS, particularly the well‐differentiated examples which are more prone to confusion with AVL; thus, lack of expression would not exclude AS . Some authors have indicated that secondary AS with MYC amplification have worse prognosis compared to cases without this molecular abnormality .…”

“…However, it is important to note that MYC amplification is not detected in all cases of secondary AS, particularly the well‐differentiated examples which are more prone to confusion with AVL; thus, lack of expression would not exclude AS . Some authors have indicated that secondary AS with MYC amplification have worse prognosis compared to cases without this molecular abnormality . Ginter et al showed that there was only 65% concordance between MYC amplification and protein expression in 20 cases of AS of other sites, in contrast to 100% concordance in 7 cases of AVL, 17 cases of primary mammary AS, and 20 cases of secondary mammary AS.…”