Development of an Immunohistochemical Assay to Detect the Ataxia-Telangiectasia Mutated (ATM) Protein in Gastric Carcinoma.

Ataxia-telangiectasia mutated (ATM), a key activator of DNA damage response mechanisms, represents a potential biomarker for targeted gastric carcinoma therapies. A phase II study (Study 39; NCT01063517) designed to investigate the combination olaparib plus paclitaxel in patients with recurrent or metastatic gastric cancer did not meet its primary endpoint of progression-free survival; however, an improvement in the secondary endpoint of overall survival was recorded with a greater overall survival benefit noted in patients with ATM-negative tumors. An ATM immunohistochemical (IHC) diagnostic assay was developed to identify patients who may respond favorably to targeted therapies and deployed in the confirmatory phase III GOLD trial (NCT01924533).

The validation of a novel method combining both HER2 immunohistochemistry and HER2 dual-colour silver in situ hybridization on one slide for gastric carcinoma testing.

Background: HER2 status assessment is a prerequisite for the establishment of an appropriate treatment strategy in gastric cancer. Gastric cancers are very heterogeneous and separate evaluations of gene amplification and protein expression lead to uncertainties in localizing distinct clones and are time consuming. This study evaluates the equivalence of the novel method combining both gene and protein platforms on one slide.

Simultaneous analysis of HER2 gene and protein on a single slide facilitates HER2 testing of breast and gastric carcinomas.

This study sought to evaluate a new combined gene and protein detection platform in the context of HER2 evaluation in breast and gastric carcinomas. HER2 immunohistochemistry (IHC) and dual color in situ hybridization (Dual ISH) were combined on a single slide. Results were compared with conventional HER2 IHC and fluorescence ISH.

Inhibition of the c-fms proto-oncogene autocrine loop and tumor phenotype in glucocorticoid stimulated human breast carcinoma cells.

The c-fms proto-oncogene encoded CSF-1 receptor and its ligand represent a feedback loop, which in a paracrine manner, is well known to promote spread of breast cancers. The role of the autocrine feedback loop in promotion of breast tumor behavior, in particular in vitro, is less well understood. The physiologic stimulation of c-fms expression by glucocorticoids (GCs) in vitro and in vivo magnifies the tumor promoting effect seen in these cells from activated c-fms signaling by CSF-1.

Posttranscriptional suppression of proto-oncogene c-fms expression by vigilin in breast cancer.

cis-acting elements found in 3'-untranslated regions (UTRs) are regulatory signals determining mRNA stability and translational efficiency. By binding a novel non-AU-rich 69-nucleotide (nt) c-fms 3' UTR sequence, we previously identified HuR as a promoter of c-fms proto-oncogene mRNA. We now identify the 69-nt c-fms mRNA 3' UTR sequence as a cellular vigilin target through which vigilin inhibits the expression of c-fms mRNA and protein.