Abstract
BackgroundThe 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.MethodsThe 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.ResultsThe 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%.ConclusionGEP-HN-LS can aid in resolving the important differential diagnosis between HNSCC and lung SCC tumors.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1753227817890930
Highlights
The differential diagnosis between metastatic head & neck squamous cell carcinomas (HNSCC) and lung squamous cell carcinomas is often unresolved because the histologic appearance of these two tumor types is similar
While patients with primary lung cancers are more likely to receive lung lobectomies, associated with a 3% mortality rate, adjuvant chemotherapy, and other aggressive forms of therapy, metastatic head & neck cancer patients are more likely to be treated with palliative chemotherapy alone [10,11]
In order to better clarify HNSCC versus lung Lung squamous cell carcinoma (SCC), we have developed a gene expression based diagnostic test, GEP-HN-LS (PathworkW Tissue of Origin Head & Neck Test, Pathwork Diagnostics, Inc., Redwood City, CA, USA), that can be used to aid in the differential diagnosis of squamous carcinomas of the head & neck and lung in FFPE tissue
Summary
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. Metastatic squamous cell carcinomas of the head & neck (HNSCC) and squamous cell carcinomas of the lung (lung SCC) appear similar on microscopic examination and are often indistinguishable using traditional histopathology. While immunohistochemical approaches are very useful in distinguishing squamous cell carcinomas from other carcinomas such as adenocarcinomas, they fail to clearly identify the site of origin of the squamous cell carcinoma [1] Both HNSCC and lung SCC show positive immunoreactivity with squamous cell carcinoma markers such as p63 and CK5/6 [2]. While patients with primary lung cancers are more likely to receive lung lobectomies, associated with a 3% mortality rate, adjuvant chemotherapy, and other aggressive forms of therapy, metastatic head & neck cancer patients are more likely to be treated with palliative chemotherapy alone [10,11]
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