A study of HER2 gene amplification and protein expression in gastric cancer.
BACKGROUND
Gastric cancer is a leading cause of cancer-related mortality, and current treatment outcomes for advanced disease remain poor. HER2 has been identified as a potential candidate for targeted therapy in gastric cancers displaying HER2 gene amplification and protein overexpression.


OBJECTIVE
To study the prevalence rate of HER2 gene amplification/overexpression in a local population, and determine the concordance rate between the various modalities.


METHODS
128 gastric cancer samples were analysed by fluorescence (FISH) and chromogenic (CISH) in situ hybridisation and immunohistochemistry (IHC). The relation between HER2 status and various clinicopathological parameters was also analysed.


RESULTS
11.7% (15/128) and 9.4% (12/128) of gastric cancers displayed HER2 gene amplification and protein overexpression (score 3+), respectively, with a perfect correlation between the FISH and CISH analyses. There was also a significant inverse correlation between overall survival and HER2 protein overexpression in intestinal-type gastric carcinomas (p<0.05).


CONCLUSIONS
Results, besides corroborating existing reports that discrepancies exist between HER2 ISH and IHC assays, also suggest the need to rigorously evaluate CISH as an independent reference standard for assessment of HER2 amplification in gastric cancers.
Yan
Benedict
B
Department of Pathology, National University Health System and National University of Singapore, Singapore, Republic of Singapore.
Yau
Ee Xuan
EX
Bte Omar
Siti Shyba
SS
Ong
Chee Wee
CW
Pang
Brendan
B
Yeoh
Khay Guan
KG
Salto-Tellez
Manuel
M
D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015203:Reproducibility of Results; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis / Q000379:methods
D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human