PIK3R1 underexpression is an independent prognostic marker in breast cancer.

Cizkova, Magdalena; Vacher, Sophie; Meseure, Didier; Trassard, Martine; Susini, Aurélie; Mlcuchova, Dana; Callens, Celine; Rouleau, Etienne; Spyratos, Frederique; Lidereau, Rosette; Bièche, Ivan

Cizkova, Magdalena; Vacher, Sophie; Meseure, Didier; Trassard, Martine; Susini, Aurélie; Mlcuchova, Dana; Callens, Celine; Rouleau, Etienne; Spyratos, Frederique; Lidereau, Rosette; Bièche, Ivan.

Afiliación

Bièche I; Oncogenetic Laboratory, Institut Curie, Hospital René Huguenin, Saint-Cloud, France. ivan.bieche@curie.net.

BMC Cancer ; 13: 545, 2013 Nov 14.

Article en En | MEDLINE | ID: mdl-24229379

RESUMEN

BACKGROUND: The present study focused on the prognostic roles of PIK3CA and PIK3R1 genes and additional PI3K pathway-associated genes in breast cancer. METHODS: The mutational and mRNA expression status of PIK3CA, PIK3R1 and AKT1, and expression status of other genes involved in the PI3K pathway (EGFR, PDK1, PTEN, AKT2, AKT3, GOLPH3, WEE1, P70S6K) were assessed in a series of 458 breast cancer samples. RESULTS: PIK3CA mutations were identified in 151 samples (33.0%) in exons 1, 2, 9 and 20. PIK3R1 mutations were found in 10 samples (2.2%) and underexpression in 283 samples (61.8%). AKT1 mutations were found in 15 samples (3.3%) and overexpression in 116 samples (25.3%). PIK3R1 underexpression tended to mutual exclusivity with PIK3CA mutations (p = 0.00097). PIK3CA mutations were associated with better metastasis-free survival and PIK3R1 underexpression was associated with poorer metastasis-free survival (p = 0.014 and p = 0.00028, respectively). By combining PIK3CA mutation and PIK3R1 expression status, four prognostic groups were identified with significantly different metastasis-free survival (p = 0.00046). On Cox multivariate regression analysis, the prognostic significance of PIK3R1 underexpression was confirmed in the total population (p = 0.0013) and in breast cancer subgroups. CONCLUSIONS: PIK3CA mutations and PIK3R1 underexpression show opposite effects on patient outcome and could become useful prognostic and predictive factors in breast cancer.

Asunto(s)

Neoplasias de la Mama/genética; Regulación Neoplásica de la Expresión Génica; Fosfatidilinositol 3-Quinasas/genética; Adulto; Anciano; Anciano de 80 o más Años; Neoplasias de la Mama/metabolismo; Neoplasias de la Mama/mortalidad; Fosfatidilinositol 3-Quinasa Clase I; Fosfatidilinositol 3-Quinasa Clase Ia; Femenino; Humanos; Persona de Mediana Edad; Mutación; Fosfatidilinositol 3-Quinasas/metabolismo; Pronóstico; Proteínas Proto-Oncogénicas c-akt/genética; Proteínas Proto-Oncogénicas c-akt/metabolismo; ARN Mensajero/genética; ARN Mensajero/metabolismo; Transducción de Señal

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Regulación Neoplásica de la Expresión Génica / Fosfatidilinositol 3-Quinasas Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: BMC Cancer Asunto de la revista: NEOPLASIAS Año: 2013 Tipo del documento: Article Pais de publicación: Reino Unido

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