V600E mutations. NGS should be carefully validated to implement this method into routine diagnostics. At the moment it is only financially feasible when the full capacity of the device is used. Conclusion To conclude, this is so far the only study comparing these five molecular methods with immunohistochemistry. We could show that Sanger sequencing BAY 734506 as a well established tool is a reliable method for BRAF mutation analysis with a limit of detection of 6. 6%. However, this method has to be replaced by faster and more cost effective methods. The cobas 4800 BRAF V600 test has limited utilization as it detects only p. V600E mutations losing 16. 3% of patients eligible for a therapy with vemurafenib.
The pyrosequencing approach showed in fact the highest sensitivity in our preselected cohort with a limit of detection of 5% mutant alleles but exhibited the lowest specificity with 90% and is prone to errors without using customer designed set up. In their present set up, the cobas 4800 BRAF V600 test as well as the Inhibitors,Modulators,Libraries therascreen BRAF Pyro Kit are therefore not sufficient for the European approval of vemurafenib because there is a therapeutic option for melanoma patients with any mutation in codon 600 of the BRAF gene. Therefore, we suggest a com bination of VE1 antibody staining and HRM for p. V600E mutation analysis combining the lowest detection limit with a fast, reliable method with 100% sensitivity for rou tine diagnostics at the moment. In the near future and with growing experiences, it is an inevitable fact that NGS will replace all established methods for molecular diagnostics.
This is based on the high sensitivity and multiplexing options of this method allowing to generate a molecular profile of each tumor sample analyzed. Background Primary small cell carcinoma of the esophagus is a specific histological Inhibitors,Modulators,Libraries type of esophageal malignancy and is a rare, aggressive disease with a high metastatic rate and poor outcome. The incidence of PSCCE is reported to be 1 1. 5% of all esophageal malignancies and from 0. 05 to 2. 4% in western populations, 7. 6% in Chinese litera ture. Several treatment options are available, includ ing surgery, Inhibitors,Modulators,Libraries chemotherapy, radiotherapy and concurrent chemo radiotherapy, but the prognosis Inhibitors,Modulators,Libraries remains poor. Hence, it is urgent to explore novel therapeutic modalities for patients with PSCCE.
Molecular targeted therapy is one of the new modal ities that have emerged in the past decade. An epidermal growth factor receptor has been Inhibitors,Modulators,Libraries validated as a promising therapeutic target for cancer. It has been re ported that EGFR expression is higher in esophageal cancer cells than in corresponding normal tissue and EGFR muta tions have always been found although the incidence is low. And whether selleck or not it may be potentially useful tar gets of therapy for esophageal cancer remains unclear.