TY - JOUR
T1 - Gastric HER2 testing study (GaTHER) : an evaluation of gastric/gastroesophageal junction cancer testing accuracy in Australia
AU - Fox, Stephen B.
AU - Kumarasinghe, Marian Priyanthi
AU - Armes, Jane E.
AU - Bilous, Michael
AU - Cummings, Margaret C.
AU - Farshid, Gelareh
AU - Fitzpatrick, Nicole
AU - Francis, Glenn D.
AU - McCloud, Philip I.
AU - Raymond, Wendy
AU - Morey, Adrienne
PY - 2012
Y1 - 2012
N2 - 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 (k=0.76), and there was good/very good agreement between IHC (positivity defined as IHC3+) and ISH when HER2 copy number was used (k=0.72 to 0.87). Agreement on CISH/SISH scoring was good/very good when HER2 copy number was used (k=0.68 to 0.86), and agreement between CISH/SISH and FISH using HER2 copy number was very good (k=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.
AB - 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 (k=0.76), and there was good/very good agreement between IHC (positivity defined as IHC3+) and ISH when HER2 copy number was used (k=0.72 to 0.87). Agreement on CISH/SISH scoring was good/very good when HER2 copy number was used (k=0.68 to 0.86), and agreement between CISH/SISH and FISH using HER2 copy number was very good (k=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.
UR - http://handle.uws.edu.au:8081/1959.7/531513
U2 - 10.1097/PAS.0b013e318244adbb
DO - 10.1097/PAS.0b013e318244adbb
M3 - Article
SN - 0147-5185
VL - 36
SP - 577
EP - 582
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 4
ER -