Relation of Hormone Receptor and Her2 Expression to Apocrine Cytology in 305 Grade III Breast Carcinomas
K Killoran, CA Axiotis, X Song, V Patel, S Bordia, K Thompson, AS Braverman. SUNY Downstate Medical Center, Brooklyn, NY; Kings County Hospital Center, Brooklyn, NY; Kings County Medical Center, Brooklyn, NY
Background: The incidence and significance of apocrine cytology (AC) in grade III breast carcinomas (BC) is uncertain. cDNA microarray studies have identified BC cases with increased androgen signaling among the Her2 molecular classes. These BC exhibit strong AC features and androgen receptor (AR) expression, suggesting a link between Her2 signaling and the "molecular apocrine" phenotype.
Design: To examine the relationship of AC to Estrogen receptor (ER) and Her2 expression in high grade BC, we identified 305 cases of grade III BC (1993-2007). All cases were evaluated for AC with standard H&E stain. Criteria for AC were 1) large cells with abundant eosinophilic cytoplasm and a N/C ratio of ≥ 1:2; 2) sharply defined cell borders; 3) large vesicular nuclei with prominent nucleoli. Her2 was determined by 3+ immunohistochemical staining (IHC) or fluorescence in-situ hybridization. ER expression was determined by IHC. Cases with > 25 % AC were tested for androgen receptor (AR) by IHC. The tumors were immunophenotyped into molecular subtypes: Luminal A (ER and/or PR+, Her2-), Luminal B (ER and/or PR+, Her2+), Her2 (ER/PR-, Her2+) or Basaloid (triple negative).
Results: 109/305 patients (36%) had AC; 83/109 were stained for AR; 26 were AR+ (31%). ER was expressed in 33/109 patients (30%) with AC, and in 120/196 without AC (61%). 25 AR+ patients 7 (28%) expressed ER, and of 3/54 AR− patients (5.6%) expressed ER. Her2 expression was known in 258 patients. 54/94 patients with AC (58%), and 73/164 without AC (45%) expressed Her2; 20/25 AR+ patients (80%) and 22/45 AR−, AC patients (49%) expressed Her2. AC+ and AC− tumors were respectively, 9.5% and 31% luminal A, 16% and 27% luminal B, 42% and 17% Her2, and 33% and 24% basaloid. 15/25 AR+ (60%) were Her2 type; AC was present in 15% luminal A, 25% luminal B, 58% Her2, and 44% basaloid tumors. 32% AC+ and 40% AC− patients' stages were III or IV, but 16/26 AR+ patients (62%) were stage III or IV.
Conclusions: AR+ tumors were distinguished from AR− AC tumors by having ≥75% AC and from tumors without AC by low ER and high Her2 expression. Most AR+ tumors were Her2 type. Grade III BC with predominant AC and AR+ may represent a distinct, aggressive pathological subtype of BC NOS whose response to therapy might be different.
Tuesday, March 23, 2010 8:15 AM
Platform Session: Section C, Tuesday Morning