Uncommon EGFR Mutations in Non-Small Cell Lung Cancer and Their Impact on the Treatment.

Background: Epidermal growth factor receptor (EGFR) mutations play an important role in the pathogenesis of non-small cell lung cancer. Because these alterations are so-called targetable mutations, their identification is important in daily clinical practice. The diagnostic standard of EGFR mutations is currently based on polymerase chain reaction methods, particularly the quantitative real-time polymerase chain reaction.

Individualization of Treatment Improves the Survival of Children With High-Risk Solid Tumors: Comparative Patient Series Analysis in a Real-Life Scenario.

The individualization of treatment is attractive, especially in children with high-risk cancer. In such a rare and very heterogeneous group of diseases, large population-based clinical randomized trials are not feasible without international collaboration. We therefore propose comparative patient series analysis in a real-life scenario.

[Malignant Melanoma - from Classical Histology towards Molecular Genetic Testing].

Background: Malignant melanoma is - in comparison with other skin tumors - a relatively rare malignant neoplasm with highly aggressive biologic behavior and variable prognosis. Recent data in pathology and molecular diagnostics indicate that malignant melanoma is in fact not a single entity but a group of different neoplasms with variable etiopathogenesis, biologic behavior and prognosis. New therapeutic options using targeted treatment blocking MAPK signaling pathway require testing of BRAF gene mutation status.

Mutational analysis of primary and metastatic colorectal cancer samples underlying the resistance to cetuximab-based therapy.

Purpose: Although several molecular markers predicting resistance to cetuximab- or panitumumab-based therapy of metastatic colorectal cancer were described, mutations in RAS proto-oncogenes remain the only predictors being used in daily clinical practice. However, 35%-45% of wild-type RAS patients still do not respond to this anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody-based therapy, and therefore the definition of other predictors forms an important clinical need. The aim of the present retrospective single-institutional study was to evaluate potential genes responsible for resistance to anti-EGFR therapy in relation to mutational analysis of primary versus metastatic lesions.

Evaluation of HER2 Gene Status in Breast Cancer Samples with Indeterminate Fluorescence in Situ Hybridization by Quantitative Real-Time PCR.

Administration of drugs targeting HER2 (official symbol ERBB2) is an important component of therapy for breast cancer patients with HER2 amplification/overexpression as determined by in situ hybridization (ISH) and immunohistochemistry (IHC). In approximately 5% of breast cancers, ISH assays fail. In these cases, HER2 protein expression is evaluated by IHC alone that may yield false negatives/positives for poor-quality samples.

A comparison of Direct sequencing, Pyrosequencing, High resolution melting analysis, TheraScreen DxS, and the K-ras StripAssay for detecting KRAS mutations in non small cell lung carcinomas.

Background: It is mandatory to confirm the absence of mutations in the KRAS gene before treating metastatic colorectal cancers with epidermal growth factor receptor inhibitors, and similar regulations are being considered for non-small cell lung carcinomas (NSCLC) and other tumor types. Routine diagnosis of KRAS mutations in NSCLC is challenging because of compromised quantity and quality of biological material. Although there are several methods available for detecting mutations in KRAS, there is little comparative data regarding their analytical performance, economic merits, and workflow parameters.

[Molecular predictive markers of EGFR-targeted therapy in metastatic colorectal cancer].

The monoclonal antibodies panitumumab and cetuximab that target the epidermal growth factor receptor are effective in approximately 10% and 20% of EGFR expressing, chemotherapy resistant metastatic colorectal cancer patients in monotherapy and in combination with chemotherapy, respectively. The evidence that EGFR expression by immunohistochemistry does not predict clinical outcome in EGFR targeted treatment has led to an intensive search for additional predicitive biomarkers. Oncogenic activation of signalling pathways downstream of the EGFR, such as mutation of KRAS, BRAF, or PIK3CA oncogenes, or inactivation of the PTEN tumor supressor gene is central to the progression of colorectal cancer.

Mutations in EGFR signal pathway in correlation with response to treatment of head and neck cancers.

Unlabelled: The prognostic and predictive value of the epidermal growth factor receptor (EGFR) expression and some genetic alterations in an EGFR signal pathway, such as the EGFR amplification, the EGFR activating tyrosine kinase domain mutations or the k-ras gene mutation were investigated in our study. The aim of the research was to evaluate the occurrence of the above-mentioned biomarkers in correlation with a therapeutic response and survival in patients with locoregionally advanced spinocellular head and neck cancers.

Keywords: Head and neck cancer, EGFR, predictive marker, k-ras, EGFR amplification, EGFR tyrosine kinase domain mutation.

The status and role of ErbB receptors in human cancer.

Changes in the expression of cellular receptors contribute to the progression of many types of solid tumors. In this review, we focus on the normal role of ErbB receptors as signal transducers and their contribution to carcinogenesis when there are abnormalities in ErbB signaling due to the overactivity of the receptors or the overexpression of ligands, which can lead to developmental defects and have been associated with many types of cancers.

Real-time PCR diagnostics failure caused by nucleotide variability within exon 4 of the human cytomegalovirus major immediate-early gene.

Here we report how variability in the human cytomegalovirus genome sequence may seriously affect the outcome of its molecular diagnosis. A real-time quantitative PCR assay targeting the major immediate-early gene failed to detect the viral load in some, but not all, clinical samples from hematooncological patients. By amplification and sequencing the DNA across the regions targeted by this assay we found a number of nucleotide substitutions which accounted for decreased primer/probe binding.