RESUMO
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.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Testes Genéticos , Neoplasias de Cabeça e Pescoço/genética , Neoplasias Pulmonares/genética , Adulto , Idoso , Algoritmos , Área Sob a Curva , Teorema de Bayes , Carcinoma de Células Escamosas/secundário , Diagnóstico Diferencial , Fixadores , Formaldeído , Perfilação da Expressão Gênica/métodos , Testes Genéticos/métodos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Razão de Chances , Análise de Sequência com Séries de Oligonucleotídeos , Inclusão em Parafina , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Fixação de TecidosRESUMO
We have developed a gene expression profile test (Pathwork Tissue of Origin Endometrial Test) that distinguishes primary epithelial ovarian and endometrial cancers in formalin-fixed, paraffin-embedded (FFPE) specimens using a 316-gene classification model. The test was validated in a blinded study using a pre-specified algorithm and microarray files for 75 metastatic, poorly differentiated or undifferentiated specimens with a known ovarian or endometrial cancer diagnosis. Measures of test performance include a 94.7% overall agreement with the known diagnosis, an area under the ROC curve (AUC) of 0.997 and a diagnostic odds ratio (DOR) of 406. Ovarian cancers (n=30) gave an agreement of 96.7% with the known diagnosis while endometrial cancers (n=45) gave an agreement of 93.3%. In a precision study, concordance in test results was 100%. Reproducibility in test results between three laboratories was 94.3%. The Tissue of Origin Endometrial Test can aid in resolving important differential diagnostic questions in gynecologic oncology.