Background Constitutive activation of HER2-dependent intracellular signalling by HER2 gene amplification or by HER2 mutations has been demonstrated as a mechanism of primary and secondary cancer resistance to cetuximab or panitumumab in preclinical and clinical models of metastatic colorectal cancer (mCRC). Both HER2 Amplification for Colorectal Cancer Enhanced Stratification (HERACLES) cohort ...

BACKGROUND Human epidermal growth factor receptor 2 (HER2) is related to the pathogenesis and poor outcome of numerous types of carcinomas, including gastric carcinoma. Gastric cancer patients with HER2 positivity have become potential candidates for targeted therapy with trastuzumab. METHODS We investigated 208 gastric cancer specimens using immunohistochemistry (IHC), fluorescence in situ h...

The recent identification of HER2 gene amplification as a novel predictor of resistance to the EGFR (HER2)-targeted antibody cetuximab and of response to combination therapies against EGFR and HER2 in wild-type KRAS tumor settings may represent a further step toward personalized medicine for patients with colorectal cancer. Herein, we show that tr...

BACKGROUND Chromogenic in situ hybridization (CISH) is fast becoming a well established technique for easy and sensitive determination of HER2 gene status in breast cancer. However, for the chromogenic method to achieve status as a safe and reliable technique, the method needs to be validated against already known and validated FISH techniques. METHODS Here it is reported from a comparative s...

Peritoneal dissemination is the most frequent metastasis in gastric cancer and is associated with poor prognosis. The lack of particular target antigens in gastric cancer other than HER2 has hampered the development of treatments for peritoneal dissemination of gastric cancer. We hypothesized that HER2-extracellular domain (HER2-ECD) gene transduction combined with trastuzumab-based photoimmuno...

BACKGROUND Positive HER2 status identifies breast carcinomas that might respond to trastuzumab treatment. Manual HER2 fluorescent in situ hybridisation (FISH) is the most readily used method to detect HER2 gene amplification which defines positive HER2 status in addition to HER2 protein overexpression. Automation of HER2 FISH may improve HER2 gene testing. The aim of our study was to evaluate a...

CONTEXT Intratumoral heterogeneity of HER2 gene amplification has been well documented and represents subclonal diversity within the tumor. The reported incidence of intratumor HER2 amplification genetic heterogeneity ranges in the literature from approximately 5% to 30%. The presence of HER2 genetic heterogeneity may increase subjectivity in HER2 interpretation by the pathologist. OBJECTIVES...

BACKGROUND HER2 and TOP2A gene status are assessed for diagnostic and research purposes in breast cancer with fluorescence in situ hybridization (FISH). However, FISH probes do not target only the annotated gene, while chromosome 17 (chr17) is among the most unstable chromosomes in breast cancer. Here we asked whether the status of specifically targeted genes on chr17 might help in refining pro...

Amplification of the HER2/neu gene in 18-20% of patients with breast cancer produces the primary mechanism of HER2 protein overexpression (PenaultLlorca et al., 2009; Thang et al., 2011; Dekker et al., 2012). The HER2 gene is a tumor marker associated with rapid tumor growth, increased recurrence rate after surgery, and decreased life expectancy (Penault-Llorca et al., 2009; Thang et al., 2011)...