With immunohistochemical stain, it was found that the rate of HER2 overexpression in www.selleckchem.com/products/arq-197.html gastric adenocarcinoma is 12% in a Japanese series (55) and 22.1% in more recent studies (56-58).
HER2 overexpression is more often noted in intestinal type carcinoma (57,59) and in the carcinomas located at proximal stomach or cardia and gastroesophageal junction (24-35%) than in the remaining stomach (9.5% to 21%) (19,59,60). In addition, HER2 status in the carcinomas of stomach and GEJ is relatively homogeneous and rarely shows significant modification from primary Inhibitors,research,lifescience,medical site to metastatic foci (61). Recently, a large scale phase III international clinical trial called ToGA showed that the humanized monoclonal antibody against HER2, Trastuzumab (Herceptin), when combined with chemotherapy (capocitabine or 5-fluorouracil and cisplatin), could effectively prolong overall Inhibitors,research,lifescience,medical survival and progression-free survival, and increases the response rate in HER2
positive advanced gastric carcinoma (57). On the basis of these findings, the regulatory approval for trastuzumab was granted in October 2010 in the United States for sellekchem patients with HER2 positive metastatic adenocarcinoma of stomach or Inhibitors,research,lifescience,medical gastroesophagical junction. Now, it is recommended that all patients with gastric cancers should routinely be tested for the HER2 status at the initial diagnosis (57,62). While HER2 positive status in gastric carcinoma is also defined as either IHC3+ or IHC2+ plus positive FISH, similar to breast cancers, there are several differences in the evaluation of HER2 status in gastric
cancers. In gastric or GEJ cancers, only 5 clustered positive cancer Inhibitors,research,lifescience,medical cells in a biopsy tissue or a minimum 10% of positive neoplastic cells in a surgical resection specimen are required for defining 3+ score, on the condition that the Inhibitors,research,lifescience,medical immunohistochemical stain reveals intense complete, basolateral, or lateral membranous reactivity (62). In order to archive accurate and reproducible HER2 scoring, it is essential that the interpretation of HER2 expression is strictly based on the criteria originally reported in the Trastuzumab for gastric cancer study, which was published and listed in Table 2 (57). Table 2 WHO 2010 Anacetrapib classification and grading of PETs (5,21) In addition, a panel of expert pathologists from the European Union and the rest of the world recommend that if immunohistochemistry is used as the initial test, any specimen type (either surgical resection or biopsy) with <10% strongly stained tumor cells should be subjected to confirmatory in situ hybridization testing to preclude false-negative results (62). If the sample is poorly preserved, shows nonspecific staining at cytoplasm and nuclei of the tumor cells, or reveals staining at benign mucosa with intestinal metaplasia, the sample should be retested by FISH to exclude false positive results (62).