Negative Estrogen Receptor and HER2 Assays at Core Biopsy of Invasive Cancers Should Be Confirmed in the Surgical Specimens.
Authors: Murray M. , Liberman L. , Nehhozina T. , Akram M. , Hassan M. , Morrow M. , Norton L. , Brogi E. 
Published: December 2010

Background: Management of patients with invasive breast carcinoma is determined by the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in the tumor cells. It is therefore critical to accurately assess ER, PR, and HER2 (ERPRH2) and avoid false-negative results that could lead to withholding of potentially beneficial therapy. Most laboratories, including ours, evaluate ERPRH2 status of invasive carcinoma on core biopsy (CB) material. We also routinely retest the cancer in 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.Methods: Retrospective review of the pathology database found 186 invasive carcinomas from 181 patients in which ERPRH2 had been performed on the CB, and negative stains repeated on the SS. For the purpose of this study, immunoperoxidase stains (IHC) were repeated simultaneously on the CB and SS for the marker with discordant result, using the same antibody. Two study pathologists reviewed all IHC. HER2 FISH was performed on the SS for all cases with a discordant HER2 IHC result.Results: The concordance rate between CB and SS results was 97.3% (181/186) and discordant results were found in 5/186 (2.7%) cases (Table 1). Three cases were discordant in ER (including 2 cases that were PR(-) on CB and SS) and two cases were discordant for HER2. Discrepancy was due to intratumoral heterogeneity in 2 cases. The CB sampled the HER2(-) area of the tumor in one case, but staining of a larger section unveiled the positive focus; the positive result was confirmed by amplification of HER2 detected by 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 had sampled the histiocytoid IL. In two other cases the discrepancy resulted from technical error. Both cases had been prospectively interpreted as ER(-) on CB and ER(+) on SS, but repeat IHC for ER showed positive staining in both the CB and SS. The fifth case was HER2 (0/1+) on CB but equivocal (1-2+) in the SS, where a larger portion of tumor was evaluated; 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(+).Conclusions: Concordance in the ER and HER2 results between CB and SS was high (97.3%), but 2.7% of cases showed discordant findings. Factors associated with discordance included intratumoral heterogeneity tumor, technical error, and equivocal findings. A triple negative profile on CB converted to either ER(+) or HER2(+) after staining on SS in 2 cases (40% of discordant cases and 1.1% of all cases), impacting patient management. Our findings suggest that any ER and/or HER2 negative result obtained at CB should be confirmed on the SS to ensure appropriate patient management.Findings of discordant casesCaseER (%)HER2HER2 FISH CBSSCBSSSS1OOO3+4.42O951+1+N/P3O1001+1+N/P45501+1+N/P590N/P0-1+1-2+2.6N/P- not performed

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6008.