_______________________________________________________________________________________________________________________________ Open Access Maced J Med Sci. 2016 Dec 15; 4(4):535-542. 535 ID Design 2012/DOOEL Skopje, Republic of Macedonia Open Access Macedonian Journal of Medical Sciences. 2016 Dec 15; 4(4):535-542. https://doi.org/10.3889/oamjms.2016.104 eISSN: 1857-9655 Basic Science Her2/neu Protein Expression and Oncogene Amplification in Gastric Carcinoma with Clinico-Pathological Correlation in Egyptian Patients Ahmed Abdel Hadi 1 , Ali El Hindawi 2 , Amal Hareedy 2 , Heba Khalil 1 , Ranya Al Ashiry 1 , Shady Elia 2 , Ahmed Sadek 1 , Mona Magdy 1 , Rafatt Atta 1 , Amgad Anas 1 , Hisham Bakr 3 , Olfat Hammam 1* 1 Theodor Bilharz Research Institute, Imbaba, Giza, Cairo, Egypt; 2 Faculty of Medicine Cairo University, Cairo, Egypt; 3 General Surgery & Surgical Oncology, Ain Shams University, Cairo, Egypt Citation: Abdel Hadi A, El Hindawi A, Hareedy A, Khalil H, Al Ashiry R, Elia S, Sadek A, Magdy M, Atta R, Anas A, Bakr H, Hammam O. Her2/neu Protein Expression and Oncogene Amplification in Gastric Carcinoma with Clinico-Pathological Correlation in Egyptian Patients. Open Access Maced J Med Sci. 2016 Dec 15; 4(4):535- 542. https://doi.org/10.3889/oamjms.2016.104 Keywords: Her2/neu; Gastric carcinoma; immunohistochemistry; fluorescence in situ hybridization; dysplasia. *Correspondence: Professor Dr. Olfat Hammam. Pathology Department, Theodor Bilharz Research Institute, El-Nile Street, Warrak El-Hadar, Imbaba P.O. Box 30, Giza 12411, Egypt. Mobile number: 202 01001815577. E-mail: totoali1@hotmail.com Received: 25-Jul-2016; Revised: 04-Sep-2016; Accepted: 05-Sep-2016; Online first: 11-Sep-2016 Copyright: © 2016 Ahmed Abdel Hadi, Ali El Hindawi, Amal Hareedy, Heba Khalil, Ranya Al Ashiry, Shady Elia, Ahmed Sadek, Mona Magdy, Rafatt Atta, Amgad Anas, Hisham Bakr, Olfat Hammam. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). Funding: This work was financed by TBRI internal project No. 94T. Principle investigator: Prof. Dr Ahmed Abdel Hadi. Competing Interests: The authors have declared that no competing interests exist. Abstract AIM: Amplification of the Her2/neu gene and overexpression of the Her2/neu protein in gastric carcinoma (GC) is a golden criterion for target therapy with trastuzumab (Herceptin). We aim to evaluate the immunohistochemical protein expression and amplification of the oncogene Her2/neu by FISH technique in the epithelial gastric carcinoma and to compare their association with different clinicopathologic parameters aiming at identifying positive cases that may benefit from targeted therapy. MATERIALS AND METHODS: This study was done on eighty-five tumour tissue samples from patients with GC as well as thirty non-malignant lesions (Gastritis, intestinal metaplasia, adenoma with low-grade dysplasia, adenoma with high-grade dysplasia). All were immunohistochemically stained with Her2/neu antibody. RESULTS: All equivocal and some selected GC cases were submitted for FISH technique to detect Her2/neu gene amplification. By immunohistochemistry twenty-three cases (27%) were defined as positive for Her2/neu gene amplification and/or protein overexpression. The levels of Her2/neu positive (3+), Her2/neu equivocal (2+) and Her2/neu negative (1+/0) were measurable in 14.2%, 32.9% and 52.9% of the samples, respectively. FISH showed that Her2/neu gene was amplified in 22 cases, 10 Her2/neu positive (3+), 11 (39.3%) Her2/neu equivocal (2+) and 1 Her2/neu negative (1+) cases with IHC staining those who can benefit from anti Her2/neu target therapy. Her2/neu was overexpressed positivity (3+) more in intestinal type and mixed carcinoma, and moderately differentiated tumours. None of gastritis, intestinal metaplasia or adenoma with low-grade dysplasia cases showed positivity for Her2/neu (3+). The Her2/neu positivity (3+) was associated with both adenocarcinoma cases and high-grade dysplasia (P = 0.002). CONCLUSIONS: The results highlight the necessity of FISH test for further categorization when gastric cancer cases are equivocal (2+) by IHC to determine eligibility for the targeted therapy. Stepwise increase in the expression of Her2/neu was seen in low-grade dysplasia, high-grade dysplasia and carcinoma cases implying its role in cancer evolution. Overexpression of Her 2/neu in GC patients can be promising in selecting those who can get benefit from anti -Her2/neu target therapy. Introduction Gastric cancer (GC) is a major cause of cancer death worldwide, especially in developing countries. The incidence of GC varies from country to country, probably as a result of genetic and environmental factors [1]. In Egypt, GC is the 12 th most common cancer in both sexes representing 1.6% of the total cancers. It is the 12 th leading cause of cancer death representing 2.2% of the total cancer mortality [2]. This is shown in many Egyptian populations- based cancer registries [3]. At the Egyptian National Cancer Institute hospital-based registry 2002–2010, GC is the 14 th most common cancer representing 1.8% of cases in both sexes [4].