Making Sense of the Her-2/neu (HER2) Immunohistochemistry (IHC) Equivocal Category Post-SCO/CAP Guidelines
AM Dastane, S Bose. UCLA, Los Angeles, CA; Cedars-Sinai Medical Center, Los Angeles, CA
Background: ASCO/CAP recently developed guidelines for HER2 testing and reporting to improve its accuracy as a predictive marker. A new equivocal IHC category was created defined as circumferential but weak membrane staining in more than 10% of cells or strong membrane staining in less than 30% of neoplastic cells. Tumors in this category are poorly defined and have uncertain benefit from anti-HER2 therapy. This study was designed to determine the characteristics of this group in comparison to the IHC positive (+) and negative (-) cases and to determine its significance as a prognostic and predictive marker.
Design: 825 consecutive cases of invasive breast carcinomas were selected from our files over a 2 year period. The HER2 IHC was performed using PathwayHer2 antibody fromVentana using Benchmark automated stainer and reported using the Ariol Scan system by Applied Imaging Corp. All the cases were also reviewed independently by two pathologists and the HER2 staining intensity and percent distribution was evaluated manually. HER2 FISH analysis was performed by the PathVysion kit and read manually. Results of IHC were correlated with the tumor characteristics, ER, PR status and HER2 FISH ratio.
Results: HER2 IHC+ carcinomas had more aggressive features as compared to the HER2 IHC- or the IHC equivocal group. Tumor characteristics of the IHC equivocal group were similar to that of the IHC- group. Chromosome 17 polysomy was more frequently observed in the IHC+ cases (21%). Further subdivision of the IHC equivocal group into FISH+ and cases confirms the resemblance of FISH- to the IHC- and FISH+ to the IHC+ group.
Comparison of HER2 IHC positive, negative and equivocal cases.NA: Not applicable;* there were 7 FISH equivocal cases
|Total cases||Grade 3 %||Mean Ki67 %||ER+ %||PR+ %||FISH+ %||Polysomy %|
|IHC equivocal FISH+*||27||62.9||42.1+/-24.7||74.1||59.3||NA||25.9|
|IHC equivocal FISH-*||94||26.6||22.9+/-21.3||93.6||75.5||NA||5.3|
Conclusions: Our study confirms the distinct phenotype of HER2+ breast carcinomas (high grade carcinomas, ER/PR-, high Ki67) as compared to HER2- carcinomas (low grade, ER/PR+, low Ki67). In the HER2 IHC equivocal group, carcinomas that are FISH+ show features similar to the HER2+ group, whereas the FISH- carcinomas show features of the HER2- group. Thus treatment of the IHC equivocal carcinomas should be based on FISH results.
Tuesday, March 10, 2009 11:15 AM
Platform Session: Section B, Tuesday Morning