Abstract
Trastuzumab has been approved for human epidermal growth factor receptor 2 (HER2)-positive advanced gastric and gastroesophageal junction cancers (GC and GJC) in combination with chemotherapy. The aim of this HER2 early/advanced gastric epidemiology (HER-EAGLE) study was to evaluate the frequency of HER2 over-expression and to evaluate agreement on HER2 status assessment in GC and GJC patients in local laboratories versus a central laboratory in China. Tumor samples from 734 GC or GJC patients who were enrolled at 11 different hospitals in China were examined. HER2 status was assessed by immunohistochemistry (IHC), and followed by dual-color silver-enhanced in Situ hybridization (DSISH) in IHC 2+ cases. Clinicopathologic characteristics were collected from all of the patients. HER2-positive tumors were identified in 12.0% (88/734) of the GC and GJC cases. There were significantly higher rates of HER2 positivity in patients with GJC (GJC: 18.1%, GC: 9.7%, P=0.002), and intestinal-type cancers using the Lauren classification (intestinal: 23.6%, diffuse/mixed: 4.3%, P<0.0001). No significant difference in HER2 positivity was identified between resection and biopsy samples, or between early and advanced disease stages. The agreement between local laboratories and the central laboratory on HER2 status scoring was good (kappa=0.86). The main reason of HER2 status discordance between local and the central laboratories was IHC result mis-interpretation in local laboratories. These results suggest that IHC followed by DSISH testing is an accurate and cost-effective procedure in China.
Highlights
Gastric cancer (GC) and gastroesophageal junction cancer (GJC) are the second most prevalent causes of cancer-related mortality worldwide [1]
Recent reports from the Trastuzumab for Gastric Cancer (ToGA) trial have shown that human epidermal growth factor receptor 2 (HER2) status (IHC 3+ or IHC 2+/ISH+) is a predictive factor of response to trastuzumab treatment in advanced GC and GJC patients [8,19]
The results from local laboratories were compared with data from the central laboratory, which participated in HER2 assessment in the ToGA trial, to explore potential problems of HER2 assessment in local laboratories
Summary
Gastric cancer (GC) and gastroesophageal junction cancer (GJC) are the second most prevalent causes of cancer-related mortality worldwide [1]. In the ad-hoc analysis of the phase III Trastuzumab for Gastric Cancer (ToGA) study, GC or GJC patients with HER2 IHC 2+/in situ hybridization positivity, or IHC 3+, achieved the greatest OS benefit (16.0 vs 11.8 months) [8]. In China, only one laboratory (Fudan University Cancer Center) has taken part in the ToGA trial and has been trained in HER2 status assessment for GC or GJC according to the update ToGA criteria. The purpose of the HER2 early/advanced gastric epidemiology (HER-EAGLE) study in Chinese population was to assess the incidence rate of HER2 positivity in GC and GJC samples that were examined by local laboratories in China and to examine the inter-laboratory reproducibility between 11 local laboratories and one central laboratory. We explored the relationship between HER2 overexpression and clinicopathological features, and common problems causing discordance of HER2 status assessment between laboratories
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