Gastric HER2 Testing Study (GaTHER): an evaluation of gastric/gastroesophageal junction cancer testing accuracy in Australia.
Trastuzumab provides a survival benefit in patients with human epidermal growth factor receptor 2 (HER2)-amplified/overexpressed advanced gastric and gastroesophageal junction cancers (GC/GJCs). However, the optimal method for testing is unclear. The aim of this study was to assess interlaboratory agreement on HER2 scoring in GC/GJC to aid the development of a robust testing algorithm for diagnostic practice in Australia. Nine laboratories assessed the HER2 status of 100 GC/GJC tissue samples by immunohistochemistry (IHC) and in situ hybridization (ISH) [chromogenic (CISH) or silver (SISH)] using both HER2 copy number and HER2:chr17 (chromosome 17) ratio. Results were compared with reference fluorescence ISH (FISH). Interlaboratory agreement on IHC3+ scoring was good (κ=0.76), and there was good/very good agreement between IHC (positivity defined as IHC3+) and ISH when HER2 copy number was used (κ=0.72 to 0.87). Agreement on CISH/SISH scoring was good/very good when HER2 copy number was used (κ=0.68 to 0.86), and agreement between CISH/SISH and FISH using HER2 copy number was very good (κ=0.88 to 0.91). Agreement was reduced when HER2:chr17 ratio was used. The good agreement for HER2 copy number determined by bright-field ISH suggests that this is the optimal method for testing in GC/GJC cases. An IHC3+ score was strongly predictive of a positive ISH result, although agreement for all IHC scores was only moderate, suggesting that IHC triage before ISH testing would be the most cost-effective strategy. However, because of the unique features of GC/GJC samples and the difficulty of ensuring consistent HER2 staining in the community setting, it is recommended that HER2 status in advanced GC/GJC be determined by both IHC and ISH in the same laboratory.
Peter MacCallum Cancer Centre, Melbourne, Vic., Australia. Stephen.Fox@petermac.org
Stephen B
SB
Fox
Marian Priyanthi
MP
Kumarasinghe
Jane E
JE
Armes
Michael
M
Bilous
Margaret C
MC
Cummings
Gelareh
G
Farshid
Nicole
N
Fitzpatrick
Glenn D
GD
Francis
Philip I
PI
McCloud
Wendy
W
Raymond
Adrienne
A
Morey
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004943:Esophagogastric Junction / Q000378:metabolism / Q000473:pathology*; D005753:Gastric Mucosa / Q000378:metabolism; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D013270:Stomach / Q000473:pathology*; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human