Dataset Information

A gene expression profile test to resolve head & neck squamous versus lung squamous cancers.

ABSTRACT: BACKGROUND: The differential diagnosis between metastatic head & neck squamous cell carcinomas (HNSCC) and lung squamous cell carcinomas (lung SCC) is often unresolved because the histologic appearance of these two tumor types is similar. We have developed and validated a gene expression profile test (GEP-HN-LS) that distinguishes HNSCC and lung SCC in formalin-fixed, paraffin-embedded (FFPE) specimens using a 2160-gene classification model. METHODS: The test was validated in a blinded study using a pre-specified algorithm and microarray data files for 76 metastatic or poorly-differentiated primary tumors with a known HNSCC or lung SCC diagnosis. RESULTS: The study met the primary Bayesian statistical endpoint for acceptance. Measures of test performance include overall agreement with the known diagnosis of 82.9% (95% CI, 72.5% to 90.6%), an area under the ROC curve (AUC) of 0.91 and a diagnostics odds ratio (DOR) of 23.6. HNSCC (N = 38) gave an agreement with the known diagnosis of 81.6% and lung SCC (N = 38) gave an agreement of 84.2%. Reproducibility in test results between three laboratories had a concordance of 91.7%. CONCLUSION: GEP-HN-LS can aid in resolving the important differential diagnosis between HNSCC and lung SCC tumors. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1753227817890930.

SUBMITTER: Lal A

PROVIDER: S-EPMC3614454 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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A gene expression profile test to resolve head & neck squamous versus lung squamous cancers.

Lal Anita A Panos Rebecca R Marjanovic Mira M Walker Michael M Fuentes Eloisa E Kubicek Gregory J GJ Henner W David WD Buturovic Ljubomir J LJ Halks-Miller Meredith M

Diagnostic pathology 20130311

<h4>Background</h4>The differential diagnosis between metastatic head & neck squamous cell carcinomas (HNSCC) and lung squamous cell carcinomas (lung SCC) is often unresolved because the histologic appearance of these two tumor types is similar. We have developed and validated a gene expression profile test (GEP-HN-LS) that distinguishes HNSCC and lung SCC in formalin-fixed, paraffin-embedded (FFPE) specimens using a 2160-gene classification model.<h4>Methods</h4>The test was validated in a blin ...[more]

PMID: 23497426

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Project description:BackgroundRegional lymph node metastasis is an important prognostic factor in head and neck squamous cell carcinoma (HNSCC) and plays a decisive role in the choice of treatment. Here, we present an independent gene expression validation study of metastasized versus non-metastasized HNSCC.MethodsWe used a dataset recently published by Roepman et al. as reference dataset and an independent gene expression dataset of 11 metastasized and 11 non-metastasized HNSCC tumors as validation dataset. Reference and validation studies were performed on different microarray platforms with different probe sets and probe content. In addition to a supervised gene-based analysis, a supervised pathway-based analysis was performed, evaluating differences in gene expression for predefined tumorigenesis- and metastasis related gene sets.ResultsThe gene-based analysis showed 26 significant differentially expressed genes in the reference dataset, 21 of which were present on the microarray platform used in the validation study. 7 of these genes appeared to be significantly expressed in the validation dataset, but failed to pass the correction for multiple testing. The pathway-based analysis revealed 23 significant differentially expressed gene sets, 7 of which were statistically validated. These gene sets are involved in extracellular matrix remodeling (MMPs, MMP regulating pathways and the uPA system), hypoxia and angiogenesis (HIF1alpha regulated angiogenic factors and HIF1alpha regulated invasion).ConclusionPathways that are differentially expressed between metastasized and non-metastasized HNSCC are involved in the processes of extracellular matrix remodeling, hypoxia and angiogenesis. A supervised pathway-based analysis enhances the understanding of the biological context of the results, the comparability of results across different microarray studies, and reduces multiple testing problems by focusing on a limited number of pathways of interest instead of analyzing the large number of probes available on the microarray.

Dataset Information

A gene expression profile test to resolve head & neck squamous versus lung squamous cancers.

Publications

A gene expression profile test to resolve head & neck squamous versus lung squamous cancers.

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