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1.
Clin Cancer Res ; 21(16): 3651-7, 2015 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-25501130

RESUMEN

PURPOSE: Scoring proliferation through Ki67 immunohistochemistry is an important component in predicting therapy response to chemotherapy in patients with breast cancer. However, recent studies have cast doubt on the reliability of "visual" Ki67 scoring in the multicenter setting, particularly in the lower, yet clinically important, proliferation range. Therefore, an accurate and standardized Ki67 scoring is pivotal both in routine diagnostics and larger multicenter studies. EXPERIMENTAL DESIGN: We validated a novel fully automated Ki67 scoring approach that relies on only minimal a priori knowledge on cell properties and requires no training data for calibration. We applied our approach to 1,082 breast cancer samples from the neoadjuvant GeparTrio trial and compared the performance of automated and manual Ki67 scoring. RESULTS: The three groups of autoKi67 as defined by low (≤ 15%), medium (15.1%-35%), and high (>35%) automated scores showed pCR rates of 5.8%, 16.9%, and 29.5%, respectively. AutoKi67 was significantly linked to prognosis with overall and progression-free survival P values P(OS) < 0.0001 and P(PFS) < 0.0002, compared with P(OS) < 0.0005 and P(PFS) < 0.0001 for manual Ki67 scoring. Moreover, automated Ki67 scoring was an independent prognosticator in the multivariate analysis with P(OS) = 0.002, P(PFS) = 0.009 (autoKi67) versus P(OS) = 0.007, PPFS = 0.004 (manual Ki67). CONCLUSIONS: The computer-assisted Ki67 scoring approach presented here offers a standardized means of tumor cell proliferation assessment in breast cancer that correlated with clinical endpoints and is deployable in routine diagnostics. It may thus help to solve recently reported reliability concerns in Ki67 diagnostics.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Antígeno Ki-67/genética , Pronóstico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores de Tumor/biosíntesis , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Proliferación Celular/genética , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Humanos , Estimación de Kaplan-Meier , Antígeno Ki-67/biosíntesis , Persona de Mediana Edad , Taxoides/administración & dosificación
2.
Cancer Lett ; 312(1): 43-54, 2011 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-21906875

RESUMEN

Pathogenetic pathways of gastrointestinal stromal tumors (GIST) lacking mutations in KIT and PDGFRA (∼15%) are still poorly studied. Nearly nothing is known about PI3K alterations in GISTs and only a few GISTs with BRAF mutations have been reported. BRAF mutations (V600E) were found in 3/87 tumors (3.5%) concomitantly were wild type for KIT and PDGFRA. No mutations were detected in KRAS, NRAS, and FGFR3. For the first-time we demonstrated a PIK3CA mutation (H1047L) simultaneously occurring with a 15-bp deletion in KIT exon 11 in one tumor. We suggest that BRAF mutations are of pathogenetic significance in wild type GISTs. The PI3K pathway should be assessed in future studies.


Asunto(s)
Tumores del Estroma Gastrointestinal/enzimología , Tumores del Estroma Gastrointestinal/genética , Mutación , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas c-kit/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Fosfatidilinositol 3-Quinasa Clase I , Análisis Mutacional de ADN , Femenino , Tumores del Estroma Gastrointestinal/patología , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas B-raf/metabolismo , Proteínas Proto-Oncogénicas c-kit/metabolismo , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Transducción de Señal
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