HER2 Status in Gastric and Gastroesophageal Junction Cancer Assessed by Local and Central Laboratories: Chinese Results of the HER-EAGLE Study

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.

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“…The discordance rate was 12.0% (305/2535) between the local and the central laboratories while it was lower between the central and the reference laboratories. Huang et al also demonstrated a similar trend in gastric cancer and they suggested that the main reason for this discrepancy was misinterpretation of the IHC score by local laboratories [11]. Methodological factors may also contribute to the discordance between laboratories, e.g.…”

“…Past studies demonstrated potential risk of falsenegative in tissue HER2 assessment for unresectable gastric cancer [9,10]. Substantial discordance in HER2 assessments among laboratories [11] as well as pathologists [12] was also reported. The HER2 receptor is composed of an intracellular domain with TK activity, a transmembrane domain and ECD.…”

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“…All the cases were histologically diagnosed and classified using the Lauren system as intestinal-type or diffuse-type gastric adenocarcinoma. Tumors exhibiting a mixed intestinal and diffuse pattern were classified as diffuse [28,29]. Stages were classified according to the 2010 GC staging system of the American Joint Committee on Cancer.…”

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“…No significant difference in HER2 positivity was identified between resection and biopsy samples, or between early and advanced disease stages [19].…”