The Importance Of Her2 In Treatment And Prognosis In Stomach Cancer (Gastric Adenocarcinoma)
Stomach cancer is characterized by a growth of cancerous cells within the lining of the stomach. Also called gastric cancer (gastric adenocarcinoma), this type of cancer is difficult to diagnose because most people typically don’t show symptoms in the earlier stages.
Human epidermal growth factor receptor 2 (HER2) overexpression is increasingly recognized as a frequent molecular abnormality in gastric and gastroesophageal cancer.
Amplification of the HER2 gene and overexpression of its product were first discovered in breast cancer and are significantly associated with worse outcomes. Many studies have demonstrated that HER2 is also present in several other malignancies, including colorectal cancer, ovarian cancer, prostate cancer, lung cancer and, particularly, gastric and gastroesophageal cancer.
A larger number of studies indicate that HER2 is a negative prognostic factor, showing more aggressive biological behavior and higher frequencies of recurrence in HER2-positive tumors. HER2 as a negative prognostic factor, suggesting that HER2 overexpression/amplification is a molecular abnormality that might be associated with the development of gastric cancer.
HER2 MOLECULAR TARGETED THERAPY
Trastuzumab is a monoclonal antibody directed against HER2; as one of the first molecular-targeted drugs to be developed, it was first introduced for the treatment of HER2-positive advanced breast cancer.
HER2 TESTING METHODS
HER2 status is mainly assessed by immunohistochemistry (IHC) or in situ hybridization (ISH) assays. Both methods can be done on formalin-fixed and paraffin-embedded biopsy tissues or surgical specimens and occasionally, cytological samples. Fluorescent in situ hybridization (FISH) is regarded to be the gold standard; however, because of its higher cost and time consumption, as well as the need for a fluorescence microscope, generally only equivocal cases are subjected to this technique. Furthermore, the high concordance between FISH and IHC that is reported in the literature supports the use of IHC, the most familiar and readily accommodated method in most surgical pathology laboratories.
In conclusion, HER2 immunohistochemistry should be studied in all gastric cancer-diagnosed gastric biopsies and / or resection specimens in terms of both the poor prognosis and the treatment protocol. In cases with suspected HER2 immunohistochemistry results, FISH should be studied.
Dr.Orkhan FARMANLI, MD
Surgical Pathologist, Istanbul/ Turkey
