HER2 Positivity in Gastroesophageal Adenocarcinoma
HER2 Positivity in Gastroesophageal Adenocarcinoma
Objectives The human epidermal growth factor receptor 2 (HER2) oncogene shows overexpression in 15% to 30% of gastroesophageal adenocarcinomas. Targeted anti-HER2 therapy with trastuzumab has been recently validated in advanced gastric and gastroesophageal junction cancer treatment. A standardized modified scoring system was recently introduced for gastroesophageal HER2 scoring. We aimed to validate this scoring system, including an analysis of interobserver variability of immunohistochemistry (IHC) scoring.
Methods In total, 323 patients with histologically confirmed invasive gastric or esophageal adenocarcinoma were examined for HER2 by IHC and chromogenic in situ hybridization (CISH). IHC 3 + or IHC 2 +/CISH positive tumors were considered HER2 positive. Interobserver variability on IHC scoring using the currently standard modified HER2 scoring system was determined among three clinical pathologists. Clinicopathologic characteristics were retrospectively retrieved from the patient records.
ResultsHER2 positivity was found in 50 (15.5%) of 323 patients. Interobserver agreement on IHC scoring was high (κ = 0.78). Most disagreement was found in diffuse or mixed tumor types and in weak to moderate stained samples (IHC 2 +). The HER2 IHC scoring system is sensitive in differentiating HER2 status before ISH.
Conclusions The currently used standardized HER2 scoring system is an excellent, clinically applicable method to establish HER2 status in appropriately educated and trained pathologists.
Gastroesophageal cancer is the second most commonly diagnosed type of cancer and is responsible for more than 1.2 million deaths every year worldwide. Adenocarcinoma is the predominant type of gastroesophageal cancer, comprising 60% to 95% of all malignant tumors.
With 5-year survival rates under 30%, the prognosis of gastroesophageal cancer remains poor. New treatment options are emerging, including targeted therapies, the most promising being the human epidermal growth factor receptor 2 (HER2/ErbB2).HER2 positivity occurs in 15% to 30% of gastroesophageal adenocarcinomas.
HER2 status in gastroesophageal adenocarcinoma is determined using a recently introduced modified scoring system, using immunohistochemistry (IHC) and in situ hybridization (ISH). IHC scoring is performed by an individual pathologist and is prone to interobserver differences, as has been shown in breast cancer and gastric cancer. Because of the higher level of tumor heterogeneity and irregular membrane staining in gastroesophageal tumors, IHC scoring is more difficult than in breast cancer, potentially giving rise to higher discordance between observers compared with breast cancer. Studies about interobserver variability in HER2 testing in gastroesophageal cancer are scarce.
Our study provides new data on interobserver variability in IHC scoring on HER2 in gastroesophageal adenocarcinoma among newly trained pathologists in a single laboratory. In addition, we analyzed interobserver variability in IHC scoring on HER2 among different primary tumor locations and histologic tumor types. The aim was to demonstrate that appropriate education and training of pathologists on the modified HER2 scoring system currently used in gastroesophageal cancer when identifying HER2 status is feasible and will result in similar interobserver variability to the other studies conducted. Furthermore, we investigated the validity of the HER2 scoring system currently used in gastroesophageal cancer for identifying HER2 status.
Abstract and Introduction
Abstract
Objectives The human epidermal growth factor receptor 2 (HER2) oncogene shows overexpression in 15% to 30% of gastroesophageal adenocarcinomas. Targeted anti-HER2 therapy with trastuzumab has been recently validated in advanced gastric and gastroesophageal junction cancer treatment. A standardized modified scoring system was recently introduced for gastroesophageal HER2 scoring. We aimed to validate this scoring system, including an analysis of interobserver variability of immunohistochemistry (IHC) scoring.
Methods In total, 323 patients with histologically confirmed invasive gastric or esophageal adenocarcinoma were examined for HER2 by IHC and chromogenic in situ hybridization (CISH). IHC 3 + or IHC 2 +/CISH positive tumors were considered HER2 positive. Interobserver variability on IHC scoring using the currently standard modified HER2 scoring system was determined among three clinical pathologists. Clinicopathologic characteristics were retrospectively retrieved from the patient records.
ResultsHER2 positivity was found in 50 (15.5%) of 323 patients. Interobserver agreement on IHC scoring was high (κ = 0.78). Most disagreement was found in diffuse or mixed tumor types and in weak to moderate stained samples (IHC 2 +). The HER2 IHC scoring system is sensitive in differentiating HER2 status before ISH.
Conclusions The currently used standardized HER2 scoring system is an excellent, clinically applicable method to establish HER2 status in appropriately educated and trained pathologists.
Introduction
Gastroesophageal cancer is the second most commonly diagnosed type of cancer and is responsible for more than 1.2 million deaths every year worldwide. Adenocarcinoma is the predominant type of gastroesophageal cancer, comprising 60% to 95% of all malignant tumors.
With 5-year survival rates under 30%, the prognosis of gastroesophageal cancer remains poor. New treatment options are emerging, including targeted therapies, the most promising being the human epidermal growth factor receptor 2 (HER2/ErbB2).HER2 positivity occurs in 15% to 30% of gastroesophageal adenocarcinomas.
HER2 status in gastroesophageal adenocarcinoma is determined using a recently introduced modified scoring system, using immunohistochemistry (IHC) and in situ hybridization (ISH). IHC scoring is performed by an individual pathologist and is prone to interobserver differences, as has been shown in breast cancer and gastric cancer. Because of the higher level of tumor heterogeneity and irregular membrane staining in gastroesophageal tumors, IHC scoring is more difficult than in breast cancer, potentially giving rise to higher discordance between observers compared with breast cancer. Studies about interobserver variability in HER2 testing in gastroesophageal cancer are scarce.
Our study provides new data on interobserver variability in IHC scoring on HER2 in gastroesophageal adenocarcinoma among newly trained pathologists in a single laboratory. In addition, we analyzed interobserver variability in IHC scoring on HER2 among different primary tumor locations and histologic tumor types. The aim was to demonstrate that appropriate education and training of pathologists on the modified HER2 scoring system currently used in gastroesophageal cancer when identifying HER2 status is feasible and will result in similar interobserver variability to the other studies conducted. Furthermore, we investigated the validity of the HER2 scoring system currently used in gastroesophageal cancer for identifying HER2 status.