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1.
Front Oncol ; 13: 1104659, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36923436

RESUMEN

Background: In the context of personalized medicine, screening patients to identify targetable molecular alterations is essential for therapeutic decisions such as inclusion in clinical trials, early access to therapies, or compassionate treatment. The objective of this study was to determine the real-world impact of routine incorporation of FoundationOne analysis in cancers with a poor prognosis and limited treatment options, or in those progressing after at least one course of standard therapy. Methods: A FoundationOneCDx panel for solid tumor or liquid biopsy samples was offered to 204 eligible patients. Results: Samples from 150 patients were processed for genomic testing, with a data acquisition success rate of 93%. The analysis identified 2419 gene alterations, with a median of 11 alterations per tumor (range, 0-86). The most common or likely pathogenic variants were on TP53, TERT, PI3KCA, CDKN2A/B, KRAS, CCDN1, FGF19, FGF3, and SMAD4. The median tumor mutation burden was three mutations/Mb (range, 0-117) in 143 patients with available data. Of 150 patients with known or likely pathogenic actionable alterations, 13 (8.6%) received matched targeted therapy. Sixty-nine patients underwent Molecular Tumor Board, which resulted in recommendations in 60 cases. Treatment with genotype-directed therapy had no impact on overall survival (13 months vs. 14 months; p = 0.95; hazard ratio = 1.04 (95% confidence interval, 0.48-2.26)]. Conclusions: This study highlights that an organized center with a Multidisciplinary Molecular Tumor Board and an NGS screening system can obtain satisfactory results comparable with those of large centers for including patients in clinical trials.

2.
Hum Pathol ; 44(10): 2116-25, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23791006

RESUMEN

Sinonasal intestinal-type adenocarcinomas (ITACs) are uncommon tumors of poor prognosis defined by their similarities to colorectal adenocarcinomas. The involvement of the epidermal growth factor receptor (EGFR) pathway in colorectal adenocarcinoma oncogenesis is well established, and the same is expected to apply to ITACs. In a series of 39 ITACs, we investigated EGFR amplification and chromosome 7 polysomy by fluorescence in situ hybridization; EGFR, KRAS, and BRAF mutational status by polymerase chain reaction sequencing; EGFR variant messenger RNA expression by quantitative reverse transcriptase polymerase chain reaction; and EGFR protein expression by immunohistochemistry with antibodies targeting the extracellular domain, the intracellular domain, and the phosphorylated isoform. The findings were analyzed with respect to clinical data, histologic typing, and patient outcome. EGFR amplification was observed in 3 cases with a focal distribution. EGFR proteins were overexpressed in all these foci with both extracellular domain and intracellular domain antibodies, suggesting involvement of the whole receptor. Chromosome 7 polysomy was observed in 15 cases and was not associated with EGFR protein expression. EGFR, KRAS, or BRAF mutations were observed in 5 different cases. The EGFRvIII mutant was not detected. In all cases, EGFR variants were expressed. There was no association between these molecular features and patient survival. In conclusion, (1) our study revealed various EGFR expression patterns in ITACs, indicating tumor heterogeneity; (2) EGFR amplification should be distinguished from chromosome 7 polysomy; (3) fluorescence in situ hybridization analysis could be guided by immunohistochemistry; and (4) ITACs share common alterations of the EGFR pathway with colorectal adenocarcinomas, except for a lower frequency of KRAS and BRAF mutations.


Asunto(s)
Adenocarcinoma/genética , Receptores ErbB/genética , Regulación Neoplásica de la Expresión Génica , Mutación , Neoplasias de los Senos Paranasales/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas/genética , Proteínas ras/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Aneuploidia , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Terapia Combinada , Femenino , Francia/epidemiología , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias de los Senos Paranasales/metabolismo , Neoplasias de los Senos Paranasales/mortalidad , Neoplasias de los Senos Paranasales/patología , Pronóstico , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas B-raf/metabolismo , Proteínas Proto-Oncogénicas p21(ras) , Estudios Retrospectivos , Tasa de Supervivencia , Proteínas ras/metabolismo
3.
Appl Immunohistochem Mol Morphol ; 17(3): 220-6, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19391220

RESUMEN

Epidermal growth factor receptor (EGFR) is produced during the molecular pathogenesis of glioma, and new anti-EGFR molecules are available for therapeutics. Consequently, analyses of the EGFR gene and protein are frequently used for glioma characterization. We compare the accuracy and the usefulness of 2 currently used techniques for histologic classification of gliomas. Fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) techniques were used to assess EGFR gene amplification and protein abundance in a series of 35 gliomas, including World Health Organization (WHO) grade I, II, and III astrocytomas (AI, AII, AIII), grade II and III tumors with oligodendroglial component (OII, OIII) and grade IV glioblastomas (GBs). EGFR gene amplification was found in one-third of the tumors studied. It was frequent in GB and OIII but was never found in AI, AII, AIII, and OII tumors. IHC and FISH provided similar findings for grade of tumor, despite the fact that, in contrast to the FISH gene amplification, EGFR protein was overexpressed in AIII and in GB. EGFR gene amplification was never observed in tumors not containing EGFR protein: therefore FISH is unnecessary when IHC shows no EGFR protein expression. EGFR gene amplification seems to be restricted to high-grade tumors, WHO grade IV astrocytomas, and grade III oligodendroglial tumors.


Asunto(s)
Neoplasias Encefálicas/patología , Receptores ErbB/metabolismo , Glioma/patología , Adolescente , Adulto , Anciano , Niño , Preescolar , Receptores ErbB/genética , Femenino , Amplificación de Genes , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Adulto Joven
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