V-ERB-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2

Alternative Names

  • ERBB2
  • Oncogene ERBB2
  • Oncogene NGL, Neuroblastoma- or Glioblastoma-Derived
  • NGL
  • NEU
  • Tyrosine Kinase-Type Cell Surface Receptor HER2
  • TKR1
  • HER2
  • Herstatin
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OMIM Number

164870

Gene Map Locus
17q21.1

Description

HER2, also known as ERBB2, is a cell surface receptor; a member of the human epidermal growth factor family of receptor tyrosine kinases. HER2 is considered to be an orphan receptor, since no ligand has been identified for this receptor to date. However, upon ligand binding to other ERBB receptors, they preferentially dimerize with HER2. This dimerization process of ERBB2 receptors is crucial for other down-stream activities to take place. Post-heterodimerization, these receptors activate several downstream signaling pathways, including the MAP kinase and PI3 pathways, resulting in activation of several protein products, including Prostate-Specific Antigen.

The HER2 gene has been found to be over-expressed in about 25-30% of breast cancers. Such cases of breast cancer have been found to be associated with increased disease recurrence and a more aggressive cancer. Research is underway in using specific medications to suppress this over-expression. Thus, HER2 expression studies are important for effective management of breast cancer. This kind of over-expression of HER2 is also noticed in some cases of ovarian cancer, prostate carcinoma, and gastric cancer.

Molecular Genetics

The HER2 gene spans a length of approximately 40 kb on the long arm of chromosome 17. The protein coded for by this gene contains 1255 amino acids and weighs about 137 kDa. As mentioned above, the protein belongs to the receptor tyrosine kinase family and the epidermal growth factor receptor subfamily. There is also a secreted form of the protein, known as herstatin.

Four different alleles of the protein have been identified, all four of which result from variations at amino acid positions 654 and 655. The most common of these alleles is Ile654/Ile655, followed by Ile-654/Val-655.

Epidemiology in the Arab World

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Other Reports

Oman

Faris et al. (2002) conducted a study to estimate the incidence of Her2/neu expression in 15 cases of breast cancer (two males, and 13 females; mean age- 47.5) in Oman and to evaluate its effect on prognosis. Of the females studied, 46% were in the pre-menopausal state. The expression of Her2/neu was determined by immunohistochemical staining using Hercep test and scores of +2 (weakly positive) and +3 (strongly positive) were taken as over-expression. The disease free period (DFP- date of surgery to date of relapse) and overall survival (OS- date of presentation to date of death) were calculated in both groups (with or without Her2/neu expression). The oncogene Her2/neu was over-expressed in eight patients (53%) and seven had negative receptors (43%). Upon analysis of the prognostic factors (TNM staging, estrogen and progesterone receptors, tumor grade and vascular invasion) among the two groups of patients, no significant difference was detected between them. Patients with Her 2/neu positive receptors had shorter DFP and OS (42 months and 69 months, respectively) when compared to those with negative receptors (10 months and 15 months, respectively). Faris et al. (2002) recommended the conduction of further prospective large scale studies to prove the preliminary results obtained, especially the high incidence of Her-2 expression. They also advised on management of patients with positive receptors with aggressive adjuvant treatment and monoclonal-targeted therapy for metastatic disease.

Al-Moundhri et al. (2003) evaluated the prognostic significance of altered expression of p53, bcl-2, HER-2/neu in Omani Arab females with non-metastatic breast cancer with correlation to other established prognostic factors. For this, a retrospective analysis for the immunohistochemical expression of p53, HER-2/neu and bcl-2 in paraffin embedded blocks was conducted for 72 females diagnosed with invasive breast cancer between 1992 and 2002. On univariate and multivariate p53 overexpression and lack of bcl-2 immunostaining resulted in worse survival outcome, but not Her-2/neu overexpression. Two years later, Al-Moundhri et al. (2005) determined the prognostic effect of HER-2/neu and other proteins in Arab patients diagnosed with gastric carcinoma and studied the association of their expression with the clinico-pathological features. HER2 expression was determined in 121 paraffin-embedded tumor blocks prepared from patients diagnosed with gastric cancer (mean age was 60.2 years, with 68.6% of the tumors being deeply penetrating T3 and T4 and 71% of the patients had advanced stages III and IV) in the period of 1995 to 2002 by immunohistochemical staining using polyclonal antibodies for HER-2/neu protein. Over-expression of HER-2/neu (more than 10% of cells exhibiting membranous staining) was found in 11.6% of the samples. A significant association between HER-2/neu and p53 was detected, and its expression correlated with histological stage, T-stage and lymph node involvement.

Qatar

Rasul et al. (2003) carried out a retrospective study to determine the prevalence of HER2/neu overexpression in Qatari women with breast cancer and to assess the survival in patients with HER2/neu positive tumors. The clinical data of 70 Qatari female patients diagnosed with breast cancer during the period 1991 through to 2001, at Hamad Medical Corporation, Doha, Qatar were reviewed. Rasul et al. (2003) also performed a retrospective review of breast tissue sample for those patients using paraffin sections and applying immunohistochemistry staining-[Hercep test (DAKO Inc)] to determine the HER2/neu status. The age of the patients at diagnosis ranged from 20 to 77 years, median (46 years). Eighteen patients (26%) were found to be HER2/neu positive (2+ and 3+) with a mean age at diagnosis of 49.3years, and 52 (74%) were found to be negative (0 and 1+) with mean age at diagnosis of 46.6 years. Of the patients with positive HER2/neu, 5 (28%) had a relapse of the disease and 4 (22%) died of the disease during follow up. Of the patients with HER2/neu negative test, 9 (17%) had a relapse of the disease and 10 (19%) died of the disease. The median survival function at mean of covariates for HER2/neu positive patients was found to be 26 months, and for HER2/NEU negative patients was found to be 28 months. Rasul et al. (2003) concluded that the prevalence of HER2/neu over expression in Qatari female with breast cancer in this study is 26%, but due to a small sample size it may not reflect really a true prevalence rate. Patients with HER2/neu positive were found to be older at diagnosis than patients with HER2/neu negative, also they had higher relapse rate and mortality. Overall median survival function was found to be better for HER2/neu negative patients than the HER2/neu positive patients.

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