Fraga-Guedes C, André S, Mastropasqua M G, Botteri E, Toesca A, Rocha R M, Peradze N, Rotmensz N, Viale G, Veronesi P, Gobbi H
Department of Anatomic Pathology, Federal University of Minas Gerais, Av Prof. Alfredo Balena, 190, Belo Horizonte, MG, 30130-100, Brazil.
Breast Cancer Res Treat. 2015 May;151(1):131-40. doi: 10.1007/s10549-015-3379-2. Epub 2015 Apr 19.
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.
MYC扩增已被报道为继发性血管肉瘤（SAS）的一个显著特征。非典型血管病变（AVL）与低级别血管肉瘤（AS）之间的鉴别诊断有时可能非常困难，甚至无法进行，而MYC扩增状态已被指出是区分乳腺皮肤血管病变的重要诊断工具。我们分别通过荧光原位杂交（FISH）和免疫组织化学（IHC）评估了49例诊断为乳腺AS的患者以及30例诊断为乳腺放疗后AVL的患者的MYC扩增和蛋白表达状态。收集了临床和病理特征以及随访数据，并进行了生存分析。在37例SAS患者中，20例患者的肿瘤具有高水平MYC扩增和蛋白过表达（54%）。原发性血管肉瘤（PAS）或AVL病例均未显示MYC扩增或蛋白表达。在AVL、PAS和SAS中，MYC扩增（FISH）与蛋白表达（IHC）之间的一致性为100%。SAS患者的生存分析表明，与无MYC扩增的病例相比，有MYC扩增的患者总生存期明显更差（P = 0.035）。有无MYC扩增的病例之间无病生存期存在非显著的不良趋势（P = 0.155）。我们的研究结果表明，MYC扩增是SAS的一种高度特异性但敏感性较差的标志物，因此，阴性结果不能排除血管肉瘤的诊断。MYC扩增与不良预后相关，提示MYC扩增状态对乳腺SAS具有预后作用。
