Epidermal Growth Factor Receptors and Topoisomerase II Alpha in Primary Adenoid Cystic Carcinomas of the Breast
S Vranic, S Frkovic-Grazio, N Bilalovic, JP Palazzo, Z Gatalica. Creighton University School of Medicine, Omaha, NE; Institute of Oncology, Ljubljana, Slovenia; University Clinical Center, Sarajevo, Bosnia and Herzegowina; Jefferson Medical Center, Philadelphia, PA
Background: Adenoid cystic carcinoma (ACC) is a rare, special subtype of breast carcinoma constituting approximately 0.1% of all breast carcinomas. Its expression profile (ER-, PR-) closely mimics that of the basal-like type of the breast carcinoma. Since there are no specific targeted therapies suitable for such tumors, research on the new potential drug targets is especially important.
Design: Twenty primary breast ACCs (19 females and 1 male) were studied for expression of epidermal growth factor receptor-1 (Her-1/EGFR), human epidermal growth factor receptor-2 (Her-2/neu), and topoisomerase II alpha (TOP2A) using immunohistochemical (IHC) and fluorescent in situ hybridization (FISH) methods.
Results: All tumors were uniformly negative for Her-2/neu protein, whereas EGFR protein was detected in the majority of cases (14/20, 70%). Topoisomerase II alpha was detected in 7/20 cases (35%) but exhibited a weak nuclear positivity in 5% or less of all tumor cells. TOP2A and EGFR gene alterations were rarely observed; only two cases exhibited gene deletions (TOP2A/CEP17 ratio 0.71, and EGFR/CEP7 ratio 0.70, respectively). No gene amplification was observed in any of the studied cases.
Conclusions: ACC of the breast is a typical triple negative, basal-like breast carcinoma with a common EGFR protein overexpression. Due to its TOP2A negativity patients with ACC of the breast are unlikely to respond to the antracycline based chemotherapy. Near uniform expression of EGFR in ACC should be further explored for targeted therapy.
Monday, March 22, 2010 1:00 PM
Poster Session II # 43, Monday Afternoon