[252] Relationship between Molecular Subtype of Invasive Breast Carcinoma (IBC) and Expression of Gross Cystic Disease Fluid Protein 15 (GCDFP), Mammaglobin (MGB), and Androgen Receptor (AR)

GH Lewis, AP Subhawong, H Nassar, R Vang, J Hicks, A De Marzo, BH Park, P Argani. Johns Hopkins Medical Institutions, Baltimore, MD

Background: IBCs can be subtyped based on gene expression into Luminal (A and B), HER2 and basal-like carcinomas (BLCs). The relative frequency of expression of GCDFP, a marker of apocrine differentiation, has not to our knowledge been assessed in these subtypes. This is particularly relevant since recent studies suggest that the HER2 subtype overlaps with a molecular apocrine subtype which expresses AR and preferentially displays "apocrine morphology," though the latter seems somewhat subjective. In addition, MGB expression has rarely been analyzed in these IBC subtypes.
Design: Tissue microarrays (TMAs) were constructed from paraffin blocks of 71 IBCs and labeled by IHC for ER, PR, HER2, CK5/6 and EGFR to subtype them as Luminal A (ER+ and/or PR+; HER2-), Luminal B (ER+ and/or PR+; HER2+), HER2 (ER, PR-; HER2+), BLC (ER-, PR-, HER2-; CK5/6 and/or EGFR+), or Unclassified Triple Negative Carcinomas (UTNC) (ER, PR, HER2, CK5/6, EGFR-). Five 1mm diameter spots per case were taken. TMA sections were labeled by IHC for GCDFP, AR, and MGB. Any labeling with these markers was considered a positive result, and correlation with subtypes was analyzed.

GCDFP, MGB and AR Immunolabeling
Cancer SubtypeGCDFPMammaglobinAR
BLC4.8% (1/21)24% (5/21)24% (5/21)
UTNC0 (0/12)17% (2/12)17% (2/12)
Luminal A65% (11/17)80% (14/17)82% (14/17)
Luminal B71% (5/7)85% (6/7)71% (5/7)
HER271% (10/14)71% (10/14)71% (10/14)

GCDFP, MGB, and AR were less likely to be expressed in BLC than in HER-2 cancers (p=0.000021, 0.013, and 0.013 respectively) or Luminal cancers (p=0.00002, 0.00008, and 0.0003 respectively). However, the difference in GCDFP, MGB, or AR expression between HER2 and Luminal cancers was not significant (p=1.0, 0.671, and 0.671 respectively).
Conclusions: Luminal cancers demonstrate similar degrees of apocrine differentiation, as assessed by GCDFP and AR immunoreactivity, as do HER2 cancers. Most BLC and UNTC are negative for both MGB and GCDFP on our TMAs, which approximate the amount of material obtained by core biopsy. Given the frequent absence of specific markers of breast origin (ER, PR, GCDFP, MGB) in BLC and UNTC, and their frequent absence of a significant associated in situ component, correlation with clinical findings may be needed to exclude the possibility of a metastasis to the breast when BLC or UTNC are encountered on core biopsy.
Category: Breast

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 24, Monday Morning


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