MYC Amplification and Overexpression in Primary Cutaneous Angiosarcoma (AS): A Fluorescence In-Situ Hybridization (FISH) and Immunohistochemical (IHC) Study of 39 Cases
Wonwoo Shon, Sarah M Jenkins, William R Sukov, Andrew L Folpe. Mayo Clinic, Rochester, MN
Background: MYC, a proto-oncogene located chromosome 8q24, is involved in control of cell proliferation and differentiation. Previous studies have documented high-level MYC gene amplification and MYC expression by IHC in post-irradiation AS, but not in primary cutaneous AS or in other radiation-associated vascular proliferations, such as atypical vascular lesions. Prompted by our recent finding of MYC amplification in a primary hepatic AS, we analyzed a large number of well-characterized primary cutaneous AS for MYC gene amplification and protein overexpression.
Design: Formalin-fixed, paraffin-embedded blocks from 39 primary cutaneous AS were retrieved from our archives and examined by IHC and FISH, using a commercially available antibody and probe. Appropriate controls were employed. For FISH, the number of copies of MYC were compared with the control gene, CEP8 (MYC/CEP8 ratio). All cases occurred on sun-exposed skin; no patient was known to have a history of therapeutic irradiation. Possible correlations with a wide variety of clinicopathological variables were evaluated using the logrank test.
Results: Cases occurred in 25 males and 14 females (median age 73 years; range 27-89 years). AS most often involved the head/neck (31), and followed by the leg (4), arm (3), and chest (1). Clinical follow-up was available on 34 (87.2 %) patients (13 dead of unknown cause, 12 dead of disease, 8 alive without disease, 1 dead of other causes; mean 4.5 yrs, range 0.13-18.9 yrs). By IHC, MYC overexpression was present in 10/39 (26%) AS-C (2-3+: 8 cases, 21%; rare cells: 2 cases, 5%). By FISH, 2/6 (33%) informative cases with 2-3+ immunostaining showed high-level gene amplification (> 8 MYC/CEP8 ratio). One additional case showed lower level amplification (≥ 2 MYC/CEP8 ratio). MYC amplification and MYC overexpression was not correlated with any of the evaluated clinicopathological parameters, including outcome.
Conclusions: We have shown, for the first time, high-level MYC gene amplification and MYC protein overexpression in primary (non-radiation-associated) AS of the skin. MYC protein overexpression in cases lacking gene amplification likely reflects other mechanisms of MYC activation. Study of a larger number of primary cutaneous AS showing high level MYC amplification will be necessary to determine whether the behavior of such cases differs from their more common non-amplified counterparts.
Monday, March 4, 2013 9:00 AM
Proffered Papers: Section F, Monday Morning