Reduced H3K27me3 expression in radiation-associated angiosarcoma of the breast
The diagnosis of radiation-associated angiosarcoma is challenging and there are overlapping clinicopathological features between radiation-associated benign, atypical and malignant vascular lesions. It has been shown convincingly, that the majority of radiation-associated angiosarcomas are characterised by amplification and subsequent overexpression of MYC in contrast to benign and atypical vascular lesions. Given the fact that epigenetic changes play an important role in carcinogenesis and loss of histone H3K27 trimethylation (H3K27me3) has been found in a number of malignant neoplasms including malignant peripheral nerve sheath tumours, especially when associated with previous radiotherapy, we evaluated the immunohistochemical reaction pattern for H3K27me3 in 49 vascular lesions and control cases: normal skin and benign vascular lesions not associated with previous radiotherapy, radiation-associated benign, atypical and malignant vascular lesions and angiosarcomas not associated with previous radiotherapy. We found loss of H3K27me3 expression in most cases of radiation-associated angiosarcomas, whereas endothelial cells in benign and atypical vascular lesions arising after previous radiotherapy stained positively for H3K27me3. The sporadic angiosarcomas stained inconsistently for H3K27me3. Loss of H3K27me3 is typically seen in radiation-associated angiosarcomas, representing an additional diagnostic tool and raises questions in regard to the carcinogenesis of malignant vascular neoplasms.
KeywordsRadiation-associated vascular lesion Radiation-associated angiosarcoma Immunohistochemistry H3K27me3
Compliance with ethical standards
The authors declare that the study has been done according to ethical standards.
Conflict of interest
The authors declare that they have no competing interests.
- 1.Kiss K, Andreasen S, Moller Talman ML, Daugaard S, Mentzel T (2017) The incidence of radiotherapy-induced angiosarcoma of the skin after treatment for breast cancer in Denmark: a population-based study. Mod Pathol 132A:517Google Scholar
- 5.Mentzel T, Schildhaus HU, Palmedo G, Büttner R, Kutzner H (2012) Postradiation cutaneous angiosarcoma after treatment of breast carcinoma is characterized by MYC amplification in contrast to atypical vascular lesions after radiotherapy and control cases: clinicopathological, immunohistochemical, and molecular analysis of 66 cases. Mod Pathol 25(1):75–85CrossRefPubMedGoogle Scholar
- 12.Bender S, Tang Y, Lindroth AM, Hovestadt V, Jones DT, Kool M, Zapatka M, Northcott PA, Sturm D, Wang W, Radlwimmer B, Hoifeldt JW, Truffaux N, Castel D, Schubert S, Ryzhova M, Seker-Cin H, Gronych J, Johann PD, Stark S, Meyer J, Milde T, Schuhmann M, Ebinger M, Monaranu CM, Ponnuswami A, Chen S, Jones C, Witt O, Collins VP, von Deimling A, Jabado N, Puget S, Grill J, Helin K, Korshunov A, Lichter P, Monje M, Plass C, Cho YJ, Pfister SM (2013) Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant paediatric high-grade gliomas. Cancer Cell 24(5):660–672CrossRefPubMedGoogle Scholar
- 16.Lee W, Teckie S, Wiesner T, Ran L, Prieto-Granada CN, Lin M, Zhu S, Cao Z, Liang Y, Sboner A, Tap WD, Fletcher JA, Huberman KH, Qin LX, Viale A, Singer S, Zheng D, Berger MF, Chen Y, Antonescu CR, Chi P (2014) PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors. Nat Genet 46(11):1227–1232CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Cleven AHG, Al Sannaa GA, Briaire-de Bruijn I, Ingram DR, van de Rijn M, Rubin B, de Vries MW, Warson KL, Torres KE, Wang WL, van Duinen SG, Hogendoorn PCW, Lazar AJ, Bovee JVMG (2016) Loss of H3K27 tri-methylation is a diagnostic marker for malignant peripheral nerve sheath tumors and an indicator for an inferior survival. Mod Pathol 29(6):582–590CrossRefPubMedPubMedCentralGoogle Scholar