Negative Estrogen Receptor and HER2 Assays at Core Biopsy of Invasive Cancers Should Be Confirmed in the Surgical Specimens
Dana Jaggessarsingh, Jeffrey Catalano, Muzaffar Akram, Edi Brogi, Melissa Murray. Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Expression of ER and HER2 in invasive breast carcinoma (IC) guides patient (pt) management. Accurate assessment is critical to avoid false-negative results and withholding of therapy. We evaluate ERH2 status on core biopsies(CB) and retest the surgical specimen(SS) for any marker negative on CB. Our study evaluates discrepancies in ER and HER2 results in CB and SS to determine if repeat testing is necessary.
Design: Review of our database found 301 IC from 306 pts in which ERH2 was performed on the CB, and negative stains repeated on the SS. For our study, immunostains(IHC) were repeated simultaneously on CB and SS for the marker with discordant results, using the same antibody. HER2FISH was done on the SS for all cases with a discordant HER2 IHC result.
Results: Concordance between CB and SS results was 98%(300/306);discordant results were found in 6/306(2%) cases (Table 1). Three cases were discordant in ER(including 2 cases that were PR(-) on CB and SS) and 3 cases were discordant for HER2. Discrepancy was due to intratumoral heterogeneity in 2 cases. CB sampled the HER2(-) area of the tumor in 1 case, but staining of a larger section unveiled the positive focus; the positve result was confirmed by HER2 FISH. The second case was an invasive lobular carcinoma(IL) with mixed classical and histiocytoid morphology; only the classical IL was ER(+), but the CB sampled the histiocytoid IL. In 2 cases discrepancy resulted from technical error. Both cases were prospectively interpreted as ER(-) on CB and ER(+) on SS, but repeat IHC for ER showed positive staining in both the CB and SS. In 2 cases HER2(0/1+) on CB but equivocal(2+) in the SS; the equivocal result led to reflex HER2 FISH with detection of low level HER2 amplification. Relying solely on the CB would have resulted in the misclassification of 2 tumors as triple negative; repeat stains on the SS showed that one was HER2(+) and the other ER(+).