Immunohistochemical Expression of Human Epidermal Growth factor Receptor-2 (HER2) In Gastric Cancer

Abstract

Summary G astric cancer is a common neoplastic disease and, more precisely, is the third leading cause of cancer death in the world, with differences amonggeographic areas (Coccolini et al., 2016). Gastric adenocarcinoma (GAC) develops in response to a combination of environmental factors and genetic alterations (Dewan et al., 2015). Atrophic gastritis (AG) and intestinal metaplasia (IM) are the most significant risk factors for gastric cancer (Yoon and Kim,2015). The Cancer Genome Atlas (TCGA) network classified gastric cancer into four subtypes: Epstein-Barr virus (EBV)-positive tumors, microsatellite instable (MSI) tumors, genomically stable (GS) tumors, and tumors with chromosomal instability (CIN)(Shmulevich,2013). Over the past half century the histologic classification of gastric carcinoma has been largely based on Lauren’s criteria, in which intestinal type and diffuse type adenocarcinoma are the two major histologic subtypes, plus indeterminate type as uncommon variant(Hwang et al., 2010). TheWHO classification (2010) recognizes four major histologic patterns of gastric cancers: tubular, papillary, mucinous and poorly cohesive (including signet ring cell carcinoma), plus uncommon histologic variants (Lauwers et al., 2010). Many gastric cancer patients present with advanced stage disease, and the prognosis remains poor (Rajagopal et al., 2015). The exceedingly poor prognosis of GAC is due to its late presentation, nonspecific symptoms like dyspepsia in early stage and limitations in treatment options (Dewan et al., 2015). Surgery with lymph node dissection is the primary treat¬ment for patients with resectablegastric cancer; however, for most patients, surgery alone is not sufficient and adjunctive therapy must be considered (Degiuli et al., 2010; Songun et al., 2010). Increased knowledge of tumor biology and the cellular and molecular mechanisms of malignant proliferation is leading to the development of targeted therapies against these specific mechanisms, in order to reduce the toxicity of traditional chemotherapic agents and improve survival. Several biological pathways have been individuated in gastric cancer. Her-2/neu (ERBB2) right now is the main molecular target where monoclonal antibodieshave been demonstrated to be effective(Coccolini et al., 2016). Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family having tyrosine kinase activity. The human epidermal growth factor receptor (HER) family of receptors plays a central role in the pathogenesis of several human cancers (Iqbal,2014). Several meta-analyses assessed the prognostic role of HER2 over-expression in gastric cancer with contrasting results (Gu et al., 2014; Kurokawa et al., 2015;Liang et al., 2014). Trastuzumab with chemotherapy is recommended as first-line therapy for patients with HER2-positive advanced or metastatic cancer, confirmed by immunohistochemistry and, if needed, by FISH for IHC 2+ (Jafferet al., 2013). The ToGA trial was the first clinical trial of targeted therapy proven to prolong survival time of patients with advanced gastric cancer, which opened a new chapter of targeted therapy for advanced gastric cancer. It laid the foundation of Her-2/neu gene detection in the diagnosis and treatment of gastric cancer and supportedthe use of trastuzumab in gastric cancer therapy(Zhu et al., 2014). This study aimed to examinethe immunohistochemical expression of Her2 protein in gastric adenocarcinoma and correlate it with different histopathological parameters, so that her2 neu assessment could be routinely donefor gastric cancer patients in Egypt and that would also help in applying trastuzumab therapy.