FISH MYC Amplification and MYC Protein Expression in Atypical Vascular Lesions, Mammary Angiosarcomas and Angiosarcomas of Other Sites
Paula S Ginter, Theresa Y MacDonald, Timothy M D'Alfonso, Rachel A Kaplan, Juan Miguel Mosquera, Mark A Rubin, Sandra J Shin. Weill Cornell Medical College, New York, NY
Background: Breast cancer patients who receive radiation therapy or develop chronic lymphedema following breast surgery are at risk for developing secondary (2o) mammary angiosarcomas (AS) and radiation-induced atypical vascular lesions (AVL). Recent studies have demonstrated MYC amplification (amp) by fluorescence in situ hybridization (FISH) in 2o mammary AS, but not in AVL, primary (1o) mammary AS or AS of other sites. Additionally, these studies have shown good concordance between MYC amp and MYC protein expression (PE) by immunohistochemistry (IHC). In this study, we aimed to identify MYC amp and PE in a sizeable cohort of mammary AS (1o and 2o), radiation-induced AVLs, and 1o AS of other sites to validate recently reported findings.
Design: Cases of AVL (n=6), 2o mammary AS (n=10), 1o mammary AS (n=17) and AS of other sites (n=19) were identified in our files. FISH analysis and IHC for MYC amp and PE, respectively, were performed on tissue microarray (TMA) or whole tissue slides. MYC amp was defined as a MYC/CEP8 ratio of ≥2.0. Strong nuclear immunoreactivity in >10% of lesional cells was deemed positive for MYC PE.
Results: All 2o mammary AS (10/10) while none of the AVL (0/6) showed MYC amplification. One of seventeen (6%) 1o mammary AS showed MYC amp. One case of cardiac AS showed MYC amp while the remaining eighteen 1o AS of other sites were not amplified (5%). MYC PE was observed in all but one 2o mammary AS (9/10). In contrast, none of the AVL (0/6) showed MYC PE. All but one 1o mammary AS (1/17=6%) were MYC negative which was also amplified. Nearly half of 1o AS of other sites (8/19=42%) showed MYC PE including the single amplified case of cardiac origin. Concordance between MYC amp and PE was 100% in cases of AVL (6/6), 1o mammary AS (17/17), and almost all 2o mammary AS (9/10). Concordance between FISH and IHC was 63% in 1o AS of other sites.
Conclusions: Our findings confirm previously published data that MYC amp by FISH is consistently present in 2o mammary AS but not in AVL, 1o mammary AS and AS of other sites. However, we have also identified MYC amp in one 1o mammary AS and one cardiac AS. These new findings suggest that MYC amp may not be specific to 2o mammary AS as previously thought. Additionally, we found that while FISH and PE was concordant in all AVL, 1o mammary AS and nearly all 2o mammary AS, this was not true in AS of other sites suggesting that while PE in mammary vascular lesions correlate highly with MYC amp, this does not hold true in non-mammary AS.
Tuesday, March 5, 2013 11:45 AM
Proffered Papers: Section B, Tuesday Morning