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Cancer ; 121(24): 4359-68, 2015 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-26488212

RESUMEN

BACKGROUND: Although colorectal mucinous adenocarcinomas (MCs) are conventionally regarded as exhibiting high-grade differentiation, they can be divided by differentiation into 2 groups according to the glandular appearance: low-grade mucinous adenocarcinoma (low-MC) and high-grade mucinous adenocarcinoma (high-MC). METHODS: Patients with colorectal cancer (CRC) who underwent surgical resection between 2000 and 2012 were enrolled in this study. Among the cases with MC, the clinicopathological and genetic differences between low-MC and high-MC were investigated with next-generation sequencing. RESULTS: A total of 1373 patients with CRC were analyzed. Forty patients (2.9%) had MC, and 13 patients had high-MC. Patients with MC had significantly shorter disease-free survival (DFS) and overall survival (OS) periods than those with nonmucinous carcinoma. When low-MC patients and high-MC patients were compared, those with high-MC had significantly shorter DFS and OS periods than those with low-MC. Multivariate analyses revealed that high-MC was significantly associated with both shorter DFS and shorter OS, but low-MC was not. A genome analysis revealed that low-MC had a considerably larger number of mutations than high-MC, and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and adenomatous polyposis coli mutations were particularly frequently found in low-MC. In contrast, SMAD family member 4 (SMAD4) mutations were frequently found in high-MC. CONCLUSIONS: High-MC is an independent prognostic factor in CRC (but low-MC is not), and it is genetically different from other CRCs, including low-MC. Both the clinicopathological differences and the genetic differences suggest that low-MC and high-MC should be distinguished in clinical settings.


Asunto(s)
Adenocarcinoma Mucinoso/genética , Proteína de la Poliposis Adenomatosa del Colon/genética , Neoplasias Colorrectales/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteína Smad4/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Proteínas de Unión al ADN/metabolismo , Supervivencia sin Enfermedad , Femenino , Células HT29 , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex , Homólogo 1 de la Proteína MutL , Proteína 2 Homóloga a MutS/metabolismo , Mutación , Clasificación del Tumor , Proteínas Nucleares/metabolismo , Pronóstico , Estudios Retrospectivos , Adulto Joven
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