[148] Significance of GRB7 Protein Expression Level in Breast Cancer

Brandon D Ellsworth, David Dabbs, Rohit Bhargava. University of Pittsburgh Medical Center, Magee-Womens Hospital, Pittsburgh, PA

Background: GRB7 is an adaptor protein that interacts with a number of signaling molecules. Although GRB7 is often co-amplified with HER2, GRB7 protein expression by immunohistochemistry (IHC) has not been widely studied, and its significance with HER2 protein expression is unknown.
Design: GRB7 protein expression was semi-quantitatively analyzed via H-score in 219 invasive breast cancers. Of the 219 cases, 195 were core biopsies (4 HER2 IHC 2+/FISH not amplified; 49 HER2 IHC 2+/FISH equivocal; 35 HER2 IHC 2+/FISH amplified; 107 HER2 IHC 3+) and 24 cancers (HER2 IHC 0 and 1+) were represented on a tissue microarray. Neo-adjuvant chemotherapy was administered in 64 cases.
Results: GRB7 H-scores were significantly higher in unequivocally HER2 amplified and IHC 3+ cases compared to HER2 equivocal and negative cases (see table 1). Higher scores also correlated with ER neg, PR neg, and high Ki-67 labeling index (>25%). No difference was identified with respect to age, tumor size, grade, or lymph node status. Of the 64 cases that received neo-adjuvant chemotherapy, 25 (39%) achieved pathologic complete response (pCR). Of these 64 cases, 55 cases were unequivocally HER2 positive (IHC 2+/FISH amplified or IHC 3+). The GRB7 score was significantly higher in tumors that achieved pCR (mean 258 compared to 192 without pCR, p=0.00005), but when these unequivocally HER2+ tumors were classified as ER-/HER2+ and ER+/HER2+, the GRB7 scores were not significantly different (see table 2).

Table 1
Groups based on HER2 resultMeanMedianRangeStd Dev; SEM
A: IHC 0 or 1+ (n=24)851000-12036; 7
B: IHC2+, FISH Namp (n=4)8710050-10025; 13
C: IHC2+, FISH Eq (n=49)1111000-26055; 8
D: IHC2+, FISH Amp (n=35)15517050-23055; 9
E: IHC3+ (n=107)2442500-30059; 6
p-values: A vs B 0.90; A vs C 0.04; A vs D <0.0001; A vs E <0.0001; B vs C 0.40; B vs D 0.02; B vs E <0.0001; C vs D 0.0005; C vs E <0.0001; D vs E <0.0001. Namp: Not Amplified; Eq: Equivocal; Amp: Amplified; SEM: Standard error of mean.

Table 2
GroupspCRNo pCRP value for GRB7 score
ER+/HER2+9 of 27 (33%) cases with mean GRB7 score of 21718 of 27 (67%) cases with mean GRB7 score of 2000.5181
ER-/HER2+16 of 28 (57%) cases with mean GRB7 score of 27212 of 28 (43%) cases with mean GRB7 score of 2420.1547
pCR: Pathologic Complete Response

Conclusions: GRB7 protein expression level parallels HER2 protein expression level and is also associated with hormone receptor negative and highly proliferative tumors. However, the predictive value of GRB7 to trastuzumab containing chemotherapy is diminished once HER2+ tumors are classified according to hormone receptor status.
Category: Breast

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 21, Monday Morning


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