Breast Cancer Molecular Class ERBB2: Preponderance of Tumors with Apocrine Differentiation and Expression of Basal Phenotype Markers CK5, CK5/6 and EGFR
R Bhargava, JM Striebel, DJ Dabbs. Magee-Womens Hospital of UPMC, Pittsburgh, PA
Background: This is a study of 205 consecutive invasive breast carcinomas (IBCs) to identify the prevalence of molecular subtypes using immunohistologic (IHC) surrogate markers. The principal aim was to identify morphologic features of tumors that belong to the molecular class ERBB2.
Design: The IBCs were classified using IHC surrogate markers-estrogen receptors (ER), progesterone receptors (PR) and HER2. ER and PR were scored using a semi-quantitative H-score like method with a dynamic range of 0-300. HER2 was considered positive only if 3+ by IHC or unequivocally amplified by FISH. The tumors were classified as follows: Luminal A (LUMA; ER score 200 or higher, HER2 negative), Luminal B (LUMB; ER score 11-199 or PR >10, HER2 negative), Triple Negative (TN; ER and PR score 10 or less, HER2 negative), ERBB2 (ER and PR score 10 or less, HER2 positive), Luminal A-HER2 Hybrid (LAHH; ER score 200 or higher, HER2 positive), Luminal B-HER2 Hybrid (LBHH; ER score 11-199 or PR >10, HER2 positive). Blocks from 197 cases were available to construct tissue microarrays (TMAs). TMAs were stained with CK5 (clone XM26). Whole tissue sections of ERBB2 tumors were stained with CK5/6 and EGFR. EGFR was scored using criterion similar to HercepTest.
*basal-like morphology in 3 cases
|Molecular Class||Prevalence||Apocrine Differentiation||CK5+|
|LUMA||55% (n=113)||4/113 (4%)||0/107 (0%)|
|LUMB||17% (n=34)||2/34 (6%)||4*/30 (13%)|
|ERBB2||4% (n=8)||7/8 (88%)||5/8 (63%)|
|TN||15% (n=32)||9/32 (28%)||22/31 (71%)|
|LAHH||5% (n=10)||2/10 (20%)||0/10 (0%)|
|LBHH||4% (n=8)||2/8 (25%)||0/8 (0%)|
Additional findings in ERBB2 tumors: Majority were high grade, with an average Nottingham score of 8. Moderate lymphoid infiltrate was seen in 5 of 8 (63%) cases and necrosis in 3 of 8 (38%) cases. The tumor cells were + for CK5/6 in 4/8 cases (50%), and showed EGFR 2+ or 3+ score in 5 cases (63%).
Conclusions: Tumors with apocrine differentiation are most often of ERBB2 type. ERBB2 tumors demonstrate some features classically ascribed to TN-basal-like tumors. EGFR overexpression in ERBB2 tumors may have predictive value (use of dual EGFR/HER2 tyrosine kinase inhibitors like lapatinib). The association between ERBB2 phenotype and apocrine morphology also likely explains the long standing enigma in breast pathology, i.e. coexistence of HER2 positive ductal carcinoma in situ (often with apocrine differentiation) and HER2 negative invasive carcinoma (without apocrine differentiation).
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 39, Tuesday Afternoon