Epidermal growth factor receptor mutation-specific immunohistochemical antibodies in lung adenocarcinoma.

Aims: We investigated the sensitivity and specificity of two novel Epidermal growth factor receptor (EGFR) mutation-specific antibodies in the detection of the most common EGFR mutations in lung adenocarcinoma.

Methods And Results: A total of 241 resected lung adenocarcinoma specimens and six resected post-neoadjuvant gefitinib adenocarcinomas were analysed for EGFR mutation using mass spectrometry, fragment analysis and direct PCR sequencing platforms. Tissue arrays and/or full sections of these cases were evaluated using immunohistochemistry with two novel antibodies (clones SP125 and SP111) and two previously reported antibodies (clones 43B2 and 6B6), specific for L858R or 15-nucleotide exon-19 deletion EGFR mutations.

Co-overexpression of Met and hepatocyte growth factor promotes systemic metastasis in NCI-H460 non-small cell lung carcinoma cells.

Complete resection of early-stage non-small cell lung cancer (NSCLC) is potentially curative, yet approximately 50% of patients are at risk for developing metastatic recurrence. Met, the receptor for hepatocyte growth factor (HGF) is a receptor tyrosine kinase with demonstrated roles in regulating cellular proliferation, motility, morphogenesis, and apoptosis. Met receptor and its ligand, HGF, are commonly overexpressed in NSCLC, and their overexpression has been associated with poor prognosis, which could potentially involve a paracrine and/or autocrine activation loop.

Gab1 but not Grb2 mediates tumor progression in Met overexpressing colorectal cancer cells.

Hepatocyte growth factor receptor (Met) plays an important role in the progression of multiple cancer types. The overexpression of Met in DLD-1 colon carcinoma cells with kirsten rat sarcoma oncogene homolog (KRAS) oncogene activation resulted in enhanced subcutaneous and orthotopic tumor growth rate and increased metastatic potential. To elucidate the mechanism of this effect, we stably expressed kinase-inactive Met(K1110A), Src homology 2 (SH2)-binding domain-inactive Met(Y1349/1356F), growth factor receptor-bound protein 2 (Grb2) non-binding Met(N1358H) and mutant receptors with ability to selectively recruit signaling proteins Grb2, src homology domain c-terminal adaptor homolog (Shc), phospholipase c-gamma (PLCgamma) and p85 phosphatidyl inositol 3 kinase.

Frequent accumulation of nuclear E-cadherin and alterations in the Wnt signaling pathway in esophageal squamous cell carcinomas.

Esophageal squamous cell carcinoma is frequently associated with poor prognosis, as a result of high levels of lymph node metastasis. So far, very few genetic abnormalities have been associated with this disease, and its molecular etiology remains largely unknown. To assess whether the Wnt pathway contributes to esophageal squamous cell carcinoma, we characterized the expression and subcellular localization of the key Wnt signaling components in all 30 cases of esophageal squamous cell carcinomas analyzed.

Integrin alpha 11 regulates IGF2 expression in fibroblasts to enhance tumorigenicity of human non-small-cell lung cancer cells.

Integrin alpha11 (ITGA11/alpha11) is localized to stromal fibroblasts and commonly overexpressed in non-small-cell lung carcinoma (NSCLC). We hypothesized that stromal alpha11 could be important for the tumorigenicity of NSCLC cells. SV40 immortalized mouse embryonic fibroblasts established from wild-type (WT) and Itga11-deficient [knockout (KO)] mice were tested for their tumorigenicity in immune-deficient mice when implanted alone or coimplanted with the A549 human lung adenocarcinoma cells.

Expression of Wnt-signaling pathway proteins in intraductal papillary mucinous neoplasms of the pancreas: a tissue microarray analysis.

Abrogation of the Wnt-signaling pathway is implicated in the carcinogenesis of several malignancies, especially colorectal cancer where up to 90% of cases are thought to have impaired Wnt signaling. It is less frequently involved in conventional ductal pancreatic adenocarcinoma. This pathway has not been explored in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas previously and formed the basis of this study.

Expression profiling by microarrays in colorectal cancer (Review).

Genome-wide gene profiling studies using microarrays have the potential to improve diagnosis and treatment of human cancers. Microarrays have identified many genes that are deregulated in colorectal cancer compared to normal tissue. Groups of genes that are predictive of tumor stage or presence of metastases, hence putatively associated with cancer progression have also been revealed.