Diagnostic utility of MYC amplification and anti-MYC immunohistochemistry in atypical vascular lesions, primary or radiation-induced mammary angiosarcomas, and primary angiosarcomas of other sites

• Published in: Human pathology Vol. 45; no. 4; pp. 709 - 716
• Main Authors: Ginter, Paula S., MD, Mosquera, Juan Miguel, MD, MSc, MacDonald, Theresa Y., BS, D'Alfonso, Timothy M., MD, Rubin, Mark A., MD, Shin, Sandra J., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2014
• Subjects: Adult; Aged; Atypical vascular lesion; Breast - pathology; Breast - radiation effects; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Female; Gene Amplification; Genes, myc - genetics; Hemangiosarcoma - diagnosis; Hemangiosarcoma - genetics; Hemangiosarcoma - metabolism; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Middle Aged; MYC; Neoplasms, Radiation-Induced - diagnosis; Neoplasms, Radiation-Induced - genetics; Neoplasms, Radiation-Induced - metabolism; Pathology; Radiation; Radiotherapy - adverse effects; Secondary angiosarcoma; Tissue Array Analysis; Young Adult; Secondary angiosarcoma; Atypical vascular lesion; MYC; Radiation
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2013.11.002

Summary Breast cancer patients who receive radiation therapy or develop chronic lymphedema following axillary dissection can develop secondary mammary angiosarcomas (ASs) and, additionally, atypical vascular lesions (AVLs) in the former group. Recently, MYC amplification by fluorescence in situ hybridization (FISH) has been identified in secondary mammary AS but not in AVL and most primary mammary AS as well as AS of other sites. We studied MYC amplification and MYC protein expression in 7 radiation-induced AVLs, 9 secondary mammary ASs, 17 primary mammary ASs, and 20 primary ASs of other sites by FISH analysis and immunohistochemistry. All 9 secondary mammary ASs showed gene amplification and protein expression, whereas neither was found in any of 7 AVLs. No MYC amplification or protein expression was identified in any of the 17 primary mammary ASs. Among primary ASs of other sites, 1 cardiac AS and 1 skin AS showed gene amplification and protein expression. The remaining 18 did not show amplification (90%), but some demonstrated protein expression (39%). We conclude that MYC amplification by FISH is present in secondary mammary AS but not in AVL. We also found MYC amplification in 1 primary skin AS and 1 primary cardiac AS. There was 100% concordance between MYC amplification and protein expression in all AVL, primary mammary AS, and secondary mammary AS, whereas only 65% concordance was found in AS of other sites. MYC protein expression in AS can be helpful in certain diagnostic scenarios in the breast but not in other sites.