Abstract

BackgroundHER2 status is a predictive biomarker of response to trastuzumab in advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. However, there is relatively little known about the role of HER2 in resected gastric or GEJ adenocarcinoma in the Western population.MethodsRetrospective, observational, single centre study of patients with gastric or GEJ adenocarcinoma undergoing surgery with curative intent between January 2007 and June 2014 in the University Hospital Complex of Santiago de Compostela. The expression of HER2 was determined by immunohistochemistry (IHC) using DAKO-HercepTest™ and gene amplification with DuoCISH using a DAKO-DuoCISH kit. The study of HER2 expression and amplification was carried out in all the patients and it was correlated with classic clinicopathological parameters, survival and recurrence pattern.Results106 patients were included. HER2 expression was as follows: 71.7% HER2 negative, 21.7% HER2 equivocal and 6.6% HER2 positive, or with HER2 overexpression. 13.2% of patients (14/106) had HER2 amplification by DuoCISH. A significant association was seen between overexpression and amplification of HER2 (p < 0.001).HER2 positivity was associated with the intestinal subtype (p = 0.010) and a low grade of differentiation (p = 0.018). Likewise, HER2 was significantly associated with a worse prognosis: overall survival (OS) 32.3 months HER2 positive versus 93.9 months HER2 negative (HR 0.42; confidence interval 95% 0.18–0.93; p = 0.028); and the presence of distant metastasis without accompanying locoregional recurrence (p = 0.048).ConclusionHER2 status defines a subgroup with differentiated clinicopathological characteristics, worse prognosis and distant dissemination, without accompanying locoregional recurrence, in patients with resected gastric or GEJ adenocarcinoma operated on in a Western population.

Highlights

  • HER2 status is a predictive biomarker of response to trastuzumab in advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma

  • HER2 status defines a subgroup with differentiated clinicopathological characteristics, worse prognosis and distant dissemination, without accompanying locoregional recurrence, in patients with resected gastric or GEJ adenocarcinoma operated on in a Western population

  • We have corroborated in this study the validity of the algorithm for determining HER2 status in advanced disease for application in gastric adenocarcinoma or resected GEJ adenocarcinoma

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Summary

Introduction

HER2 status is a predictive biomarker of response to trastuzumab in advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. Surgery is the treatment of choice in resectable gastric adenocarcinoma. In locally advanced resectable tumours, 5-year survival rates remain poor, ranging between 10% and 50%, so complementary treatment strategies are needed [2]. Various strategies, such as perioperative chemotherapy, adjuvant chemotherapy or chemoradiotherapy have been tested with an absolute benefit in terms of OS around 10%–15%, but to date there is no unanimity on which strategy to use [3,4,5,6]. The HER2 receptor has been widely studied, first in breast cancer and more recently in gastric cancer [7]

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