title: Her2/neu Protein Expression and Oncogene Amplification in Gastric Carcinoma with Clinico-Pathological Correlation in Egyptian Patients.
abstract: OBJECTIVE
  Amplification of the Her2/neu gene and overexpression of theHer2/neuprotein 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.
  
  
  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 detectHer2/neugene amplification. By immunohistochemistry twenty-three cases (27%) were defined as positive forHer2/neugene 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 thatHer2/neugene 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/neuwas 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.
authors.affiliation: Theodor Bilharz Research Institute, Imbaba, Giza, Cairo, Egypt.
authors.forename: Ahmed Abdel
authors.initials: AA
authors.lastname: Hadi
authors.affiliation: Faculty of Medicine Cairo University, Cairo, Egypt.
authors.forename: Ali El
authors.initials: AE
authors.lastname: Hindawi
authors.affiliation: Faculty of Medicine Cairo University, Cairo, Egypt.
authors.forename: Amal
authors.initials: A
authors.lastname: Hareedy
authors.affiliation: Theodor Bilharz Research Institute, Imbaba, Giza, Cairo, Egypt.
authors.forename: Heba
authors.initials: H
authors.lastname: Khalil
authors.affiliation: Theodor Bilharz Research Institute, Imbaba, Giza, Cairo, Egypt.
authors.forename: Ranya Al
authors.initials: RA
authors.lastname: Ashiry
authors.affiliation: Faculty of Medicine Cairo University, Cairo, Egypt.
authors.forename: Shady
authors.initials: S
authors.lastname: Elia
authors.affiliation: Theodor Bilharz Research Institute, Imbaba, Giza, Cairo, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Sadek
authors.affiliation: Theodor Bilharz Research Institute, Imbaba, Giza, Cairo, Egypt.
authors.forename: Mona
authors.initials: M
authors.lastname: Magdy
authors.affiliation: Theodor Bilharz Research Institute, Imbaba, Giza, Cairo, Egypt.
authors.forename: Rafatt
authors.initials: R
authors.lastname: Atta
authors.affiliation: Theodor Bilharz Research Institute, Imbaba, Giza, Cairo, Egypt.
authors.forename: Amgad
authors.initials: A
authors.lastname: Anas
authors.affiliation: General Surgery & Surgical Oncology, Ain Shams University, Cairo, Egypt.
authors.forename: Hisham
authors.initials: H
authors.lastname: Bakr
authors.affiliation: Theodor Bilharz Research Institute, Imbaba, Giza, Cairo, Egypt.
authors.forename: Olfat
authors.initials: O
authors.lastname: Hammam
keywords: Gastric carcinoma; Her2/neu; dysplasia; fluorescence in situ hybridization; immunohistochemistry