Invasive Apocrine Carcinomas Are Molecularly Diverse Group of Breast Cancers
Z Gatalica, S Vranic. Creighton University School of Medicine, Omaha, NE
Background: Extensive apocrine differentiation (large epithelial cells with prominent eosinophilic, flocculent cytoplasm, sharply defined cell borders, and with large nuclei containing prominent macronucleoli) is seen in approximately 5% of all breast cancers. Recent gene expression studies recognized a characteristic “molecular apocrine” gene expression profile in these tumors, different from common luminal and basal-like breast carcinoma subtypes. However, a practical, routine diagnostic and prognostic sub-classification of apocrine carcinomas is not known.
Design: A cohort of 55 female patients with invasive apocrine carcinomas was evaluated for the expression of estrogen receptor-alpha (ER), progesterone receptor (PR), androgen receptor (AR), Her-2/neu, and EGFR using routine immunohistochemical methods. Additionally, HER2 and EGFR gene copy number was assessed using fluorescent in-situ hybridization (FISH).
Results: Of 55 cases, thirty-eight (69.1%) expressed a characteristic steroid receptor profile (ER-, PR-, AR+) of pure apocrine carcinoma (PAC). The remaining 17 cases (30.9%) lacked this specific profile (apocrine-like carcinomas, ALC): ALC with ER+/AR- phenotype (3 cases), ALC with ER-/AR- phenotype (4 cases), and ALC with ER+/AR+ phenotype (10 cases). Her-2/neu protein overexpression (3+) was observed in about half of the cases in the entire cohort (53.7%) without significant difference between the PAC and ALC groups (56.8% vs. 47.1%, p=0.81). EGFR was expressed (1+ to 3+) in 61.9% of all cases. A significantly higher proportion of PACs was positive for EGFR protein in comparison with the ALC subgroups (76.3% vs. 29.4%, p=0.006). A statistically significant inverse correlation between EGFR and Her-2/neu expression was seen in the PAC (p=0.006, r=-.499). HER-2/neu FISH results were concordant with Her-2/neu immunohistochemistry results in 92.5% cases. EGFR gene amplification was a rare event, present only in three (2 PAC and 1 ALC tumors) of 44 cancers (6.8%)
Conclusions: Breast carcinomas with apocrine differentiation are very heterogeneous in molecular terms. 52.6% of PAC cases can be classified as HER-2-overexpressing, and 47.4% as triple-negative breast carcinomas. 94.4% of triple negative PAC overexpressed EGFR and could accordingly be classified as basal-like breast carcinoma. A majority (76.5%) of ALC belonged to the luminal group. These results translate into a different prognosis for individual patients with “apocrine” carcinoma.
Tuesday, March 23, 2010 8:00 AM
Platform Session: Section C, Tuesday Morning