Abstract
Background: Patients with gastric cancer (GC) have a poor survival and biologicals such as Trastuzumab have not been used routinely in these patients. Existing data on HER2 expression and its clinical relevance in GC are still limited and controversial.Methods: HER2 expression was investigated by immunohistochemistry in 418 GC from Germany and 506 GC from England. Results were compared to clinicopathological parameters and patient survival.Results: Less than 10% of all GC showed HER2 expression in more than 5% of tumour cells and 91% of these were intestinal type GC. In both series, no relationship was found between HER2 expression, patient survival or TNM stage. Marked intratumoural heterogeneity was noted.Conclusions: This is the largest study to date demonstrating in two independent series that HER2 expression is not related to gastric cancer patient prognosis and that only a very small subgroup of intestinal type GC may potentially respond to HER2 targeting therapy. Due to prominent intratumoural heterogeneity of HER2 expression in GC, HER2 testing in endoscopic biopsies before treatment will be prone to false negative results.
Highlights
The incidence of gastric cancer (GC) has halved since the 1940s in Western countries, GC remains an important health issue and is the 4th commonest malignancy in the world [15]
Trastuzumab is a monoclonal antibody directed against the extracellular domain of the HER2 protein and has demonstrated efficacy in GC cell lines [9,17] as well as xenograft models of GC [7,21]
Our study aims were (i) to assess whether the so called “DAKO-Score” which was originally developed for breast cancer is suitable for HER2 scoring in GC; (ii) to investigate the frequency and intratumoural distribution of membranous HER2 expression in two large series of primary GC from two different countries; and (iii) to analyse the association of HER2 expression with clinicopathological parameters and patient survival
Summary
The incidence of gastric cancer (GC) has halved since the 1940s in Western countries, GC remains an important health issue and is the 4th commonest malignancy in the world [15]. Even with additional chemotherapy or chemoradiation, the median five year survival of patients with curatively resectable GC is still poor with 23% and 35%, respectively [3,29]. With the advent of “targeted therapies” it seems to be necessary to evaluate whether these new therapies could potentially be of benefit to GC patients by (i) establishing the frequency of expression of the potential target and (ii) investigating whether methods of predictive testing established for cancers of other organs are appropriate to be used in patients with GC. Studies in primary breast cancer demonstrated that patients will only potentially respond to Trastuzumab treatment if tumour cells overexpress HER2 in the cell membrane and/or show HER2 gene amplification [36]. HER2 expression has been studied in relatively small series of. Patients with gastric cancer (GC) have a poor survival and biologicals such as Trastuzumab have not been used routinely in these patients. Existing data on HER2 expression and its clinical relevance in GC are still limited and controversial
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