HER-2/ERBB2 amplification (17q11.2-12)
HER-2/neu gene, also known as ERBB2 or HER2, encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases, which plays a role in cell growth and is amplified and overexpressed in 20–30% of cases of primary human breast. Besides breat cancer, HER2 is also overexpressed/amplified in a range of tumor types including ovarian, bladder, salivary gland, endometrial, pancreatic and non-small-cell lung cancer (NSCLC). This gene encodes a 185 Kb membrane receptor protein member of the tyrosine kinase family.
Amplification of the HER-2/neu gene (17q11.2-12) is detected by fluorescence in situ hybridization (FISH) in FFPE tissue samples of breast cancer and gastric cancer. This test is indicated in the evaluation of patients for consideration for treatment with the monoclonal antibody Herceptin (Trastuzumab), which increases patient survival by blocking overexpressed HER2 protein. The obtained results, together with existing clinical and pathologic data, are a prognostic factor in patients with breast cancer. In conjunction with other available prognostic factors, it is useful to predict disease-free interval and overall survival in patients with breast cancer and nodal involvement in stage II treated with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF). Any other available clinical and pathological information such as tumor size, number of lymph nodes involved and steroid receptor status must be taken into account when making treatment decisions with adjuvant CAF. Treatment decisions should not be taken on these patients only on the basis of status amplification of the HER-2/neu gene.
Overexpression and amplification of ERBB2 are frequently observed in Esophageal Carcinoma Squamous Cell. Some meta-analysis shows that there is a high prevalence rate of HER2+ in both Barrett’s Esophagus and Esophageal Cancer populations, 24% and 26%, respectively. HER2+ prevalence in both BE and EC was relatively high with approximately a forth of patients indicating HER2+. HER2+ in EC has been shown to decrease survival. HER2+ targeted therapy for eligible patients should be considered and carried out in a clinical trial. The FDA granted approval for trastuzumab in combination with cisplatin and a fluoropyrimidine (capecitabine or 5-fluorouracil) for the treatment of patients with HER2-overexpressing metastatic gastric or gastroesophageal adenocarcinoma who have not received previous treatment for metastatic disease.
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