Her2/neu protein expression and oncogene amplification in gastric carcinoma with clinico-pathological correlation in Egyptian patients

Theodor Bilharz Research Institute

Bibliographic Information

Authors: 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.

Journal: Open Access Macedonian Journal of Medical Sciences

Publication Date: 14 September 2016

Volume / Issue: Volume 4 / Issue 4

Pages: 535–542

ISSN: 18579655

DOI: 10.3889/oamjms.2016.104

Scopus: View on Scopus

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access


Authors and Affiliations

Abdel Hadi A., Theodor Bilharz Research Institute, Imbaba, Giza, Cairo, Egypt; El Hindawi A., Faculty of Medicine Cairo University, Cairo, Egypt; Hareedy A., Faculty of Medicine Cairo University, Cairo, Egypt; Khalil H., Theodor Bilharz Research Institute, Imbaba, Giza, Cairo, Egypt; Al Ashiry R., Theodor Bilharz Research Institute, Imbaba, Giza, Cairo, Egypt; Elia S., Faculty of Medicine Cairo University, Cairo, Egypt; Sadek A., Theodor Bilharz Research Institute, Imbaba, Giza, Cairo, Egypt; Magdy M., Theodor Bilharz Research Institute, Imbaba, Giza, Cairo, Egypt; Atta R., Theodor Bilharz Research Institute, Imbaba, Giza, Cairo, Egypt; Anas A., Theodor Bilharz Research Institute, Imbaba, Giza, Cairo, Egypt; Bakr H., General Surgery & Surgical Oncology, Ain Shams University, Cairo, Egypt; Hammam O., Theodor Bilharz Research Institute, Imbaba, Giza, Cairo, Egypt


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. © 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.


Keywords

Dysplasia; Fluorescence in situ hybridization; Gastric carcinoma; Her2/neu; Immunohistochemistry; epidermal growth factor receptor 2; Article; chemoradiotherapy; gastritis; gene amplification; gene overexpression; histopathology; human; human tissue; intestine metaplasia; major clinical study; oncogene; partial gastrectomy; protein expression; stomach adenocarcinoma; stomach cancer; tumor cell; tumor differentiation


Citation Information

Scopus Citations: 6


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