HER2 Status in Gastric Cancer: Correlation between IHC and FISH
LJ Tafe, M Zaidinski, C Hedvat, L Tang, Y Janjigian, M Shah, V Barbashina. Memorial Sloan-Kettering Cancer Center, New York City, NY
Background: Patients with advanced gastric cancer (GC) have poor survival with current therapy. In a subset of GC, HER2 represents a new promising therapeutic target. HER2 is a proto-oncogene that encodes a transmembrane tyrosine kinase receptor. The oncogenic conversion of HER2 commonly occurs through gene amplification which results in protein overexpression. The results of the ToGA phase III clinical trial (Van Cutsem, 2009 ASCO) demonstrated the benefit of trastuzumab when added to standard chemotherapy in patients with HER2 positive GC, a finding that is expected to make significant impact on clinical practice. The optimal HER2 testing strategy in GC is not yet defined. We sought to evaluate the concordance between IHC and FISH to determine if breast cancer scoring criteria and algorithm are applicable to GC.
Design: FFPE tumor samples from advanced stage GC (stomach or gastroesophageal junction/ distal esophagus) were tested by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). IHC was performed with Ventana PATHWAY rabbit monoclonal antibody (clone 4B5). FISH was performed using the PathVysion HER2 assay and procedure (Vysis/Abbott). IHC and FISH results were scored according to the ASCO/CAP guidelines for breast cancer.
Results: Results on the first 40 cases are available (the study is ongoing). This includes 31 biopsy and 9 resection specimens among which 30 were primary tumors, 1 was a recurrence and 9 were metastases. Seven (17.5%) cases showed HER2 amplification, which correlated well with 3+ IHC scores. The overall concordance rate between IHC and FISH was 93%. There was a trend for higher positivity rate (IHC 3+/ FISH+) in moderately differentiated intestinal type tumors, particularly those located in the gastic antrum and GEJ/distal esophagus. Equivocal IHC (2+) and FISH results (1.8 – 2.2) were relatively uncommon (7.5% and 2.5%, respectively).
|FISH||IHC 0||IHC 1+||IHC 2+||IHC 3+||Total|
|Positive (HER2/CEP17 ratio > 2.2)||-||1 (2.5%)||1 (2.5%)||5 (12.5%)||7 (17.5%)|
|Negative (HER2/CEP17 ratio < 1.8)||20 (50%)||11 (27.5%)||1 (2.5%)||-||32 (80%)|
|Equivocal (HER2/CEP17 ratio 1.8 - 2.2)||-||-||1 (2.5%)||-||1 (2.5%)|