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1.
Cancer Med ; 6(5): 883-901, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28371134

RESUMEN

Comprehensive genetic profiling of tumors using next-generation sequencing (NGS) is gaining acceptance for guiding treatment decisions in cancer care. We designed a cancer profiling test combining both deep sequencing and immunohistochemistry (IHC) of relevant cancer targets to aid therapy choices in both standard-of-care (SOC) and advanced-stage treatments for solid tumors. The SOC report is provided in a short turnaround time for four tumors, namely lung, breast, colon, and melanoma, followed by an investigational report. For other tumor types, an investigational report is provided. The NGS assay reports single-nucleotide variants (SNVs), copy number variations (CNVs), and translocations in 152 cancer-related genes. The tissue-specific IHC tests include routine and less common markers associated with drugs used in SOC settings. We describe the standardization, validation, and clinical utility of the StrandAdvantage test (SA test) using more than 250 solid tumor formalin-fixed paraffin-embedded (FFPE) samples and control cell line samples. The NGS test showed high reproducibility and accuracy of >99%. The test provided relevant clinical information for SOC treatment as well as more information related to investigational options and clinical trials for >95% of advanced-stage patients. In conclusion, the SA test comprising a robust and accurate NGS assay combined with clinically relevant IHC tests can detect somatic changes of clinical significance for strategic cancer management in all the stages.


Asunto(s)
ADN de Neoplasias/genética , ADN de Neoplasias/metabolismo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Inmunohistoquímica/métodos , Neoplasias/terapia , Análisis de Secuencia de ADN/métodos , Línea Celular Tumoral , Variaciones en el Número de Copia de ADN , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Polimorfismo de Nucleótido Simple , Reproducibilidad de los Resultados , Nivel de Atención , Translocación Genética
2.
Am J Clin Pathol ; 129(6): 894-8, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18480005

RESUMEN

Merkel cell carcinoma (MCC) is a high-grade neuroendocrine carcinoma of skin characterized by cells with a "blastic" appearance, scant cytoplasm, and fine, evenly distributed chromatin. Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase present in thymic T cells, lymphoblastic lymphoma/leukemia, and some cases of acute myeloid leukemia. After observing TdT immunoreactivity in a case of MCC, we analyzed 26 tumors by immunohistochemical analysis to determine their spectrum of reactivity with TdT and identified TdT in 19 (73%) of 26 MCCs. Staining intensity was variable but was often moderate to strong and present in a significant percentage of cells. Because MCC has cytomorphologic features similar to those of lymphoblastic lymphoma and may manifest as metastatic disease, reactivity with TdT in MCC could represent a diagnostic pitfall in the differential diagnosis with lymphoblastic lymphoma, particularly because the latter may lack CD45 and/or CD20, yet both neoplasms may express PAX-5, a B-cell-associated marker.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células de Merkel/enzimología , ADN Nucleotidilexotransferasa/metabolismo , Neoplasias Cutáneas/enzimología , Anciano , Anciano de 80 o más Años , Antígenos CD20/metabolismo , Carcinoma de Células de Merkel/patología , Diagnóstico Diferencial , Femenino , Humanos , Técnicas para Inmunoenzimas , Antígenos Comunes de Leucocito/metabolismo , Masculino , Persona de Mediana Edad , Factor de Transcripción PAX5/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimología , Neoplasias Cutáneas/patología
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