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).
|Groups based on HER2 result||Mean||Median||Range||Std Dev; SEM|
|A: IHC 0 or 1+ (n=24)||85||100||0-120||36; 7|
|B: IHC2+, FISH Namp (n=4)||87||100||50-100||25; 13|
|C: IHC2+, FISH Eq (n=49)||111||100||0-260||55; 8|
|D: IHC2+, FISH Amp (n=35)||155||170||50-230||55; 9|
|E: IHC3+ (n=107)||244||250||0-300||59; 6|
|Groups||pCR||No pCR||P value for GRB7 score|
|ER+/HER2+||9 of 27 (33%) cases with mean GRB7 score of 217||18 of 27 (67%) cases with mean GRB7 score of 200||0.5181|
|ER-/HER2+||16 of 28 (57%) cases with mean GRB7 score of 272||12 of 28 (43%) cases with mean GRB7 score of 242||0.1547|