2 research outputs found

    New Methods for ALK Status Diagnosis in Non–Small-Cell Lung Cancer: An Improved ALK Immunohistochemical Assay and a New, Brightfield, Dual ALK IHC–In Situ Hybridization Assay

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    Introduction:The demonstration of anaplastic lymphoma kinase (ALK) positivity in non–small-cell lung cancer (NSCLC) has been hindered by the technical complexity and interpretative challenges of fluorescence in situ hybridization methods for detection of ALK gene rearrangement and by the inadequate sensitivity of existing immunohistochemistry (IHC) methods for ALK protein detection. In this study, we sought to increase the sensitivity of ALK IHC detection and to develop a brightfield assay for concurrent detection of ALK protein expression and ALK gene rearrangement.Methods:We developed a horseradish peroxidase–based IHC detection system using the novel, nonendogenous hapten 3-hydroxy-2-quinoxaline (HQ) and tyramide. We also developed a dual gene protein ALK assay combining a brightfield break-apart in situ hybridization ALK assay with another sensitive IHC method using the novel, nonendogenous hapten 5-nitro-3-pyrazole. We examined the sensitivity and accuracy of these methods using surgically resected NSCLC cases examined with ALK fluorescence in situ hybridization.Results:The new HQ-tyramide IHC detection system offered readily interpretable staining with substantially greater sensitivity than conventional ALK IHC, and produced heterogeneous and homogeneous patterns of ALK protein staining among ALK-positive NSCLC surgical cases. The new 5-nitro-3-pyrazole–based IHC detection system was similar in ALK detection sensitivity to the HQ-tyramide IHC system and was compatible with the brightfield in situ hybridization assay.Conclusion:The new HQ-tyramide IHC reagent system allows more sensitive assessment of ALK protein status in NSCLC cases. The new ALK gene-protein assay allows the concurrent visualization of ALK gene and ALK protein status in single cells, allowing more accurate ALK status determination even in heterogeneous specimens

    Are cost-inclusive evaluations worth the effort?

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    Relative costs are as important as relative effectiveness when choosing between program alternatives or among a set of programs competing for scarce funds. Nevertheless, the number of cost-inclusive evaluations remains comparatively small. This article presents the results of three first-time cost-inclusive evaluations each performed by an experienced evaluator. Each evaluator performed a different type of cost-inclusive evaluation using different tobacco control programs as examples: "standard" cost-effectiveness analysis, threshold or break-even analysis, and a simulation model. Results are presented in terms of the challenges faced, and informational and insight benefits gained, as well as in terms of program cost-effectiveness. All three evaluators agreed that the benefits from performing cost-inclusive evaluations are well worth time and effort involved. They also found that this type of evaluation provides abundant information that can be used to improve program effectiveness and cost-effectiveness.Cost-effectiveness Cost-benefit Efficiency Break-even Simulation model Tobacco control
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