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Clinical Impact and Prognostic Role of KRAS/BRAF/PIK3CA Mutations in Stage I Colorectal Cancer.
Reggiani Bonetti, Luca; Barresi, Valeria; Maiorana, Antonino; Manfredini, Samantha; Caprera, Cecilia; Bettelli, Stefania.
Afiliación
  • Reggiani Bonetti L; Department of Diagnostic Medicine and Public Health, Section of Pathology, University of Modena and Reggio Emilia, Modena, Italy.
  • Barresi V; Department of Pathology, University of Messina, Messina, Italy.
  • Maiorana A; Department of Diagnostic Medicine and Public Health, Section of Pathology, University of Modena and Reggio Emilia, Modena, Italy.
  • Manfredini S; Department of Diagnostic Medicine and Public Health, Section of Pathology, University of Modena and Reggio Emilia, Modena, Italy.
  • Caprera C; Department of Diagnostic Medicine and Public Health, Section of Pathology, University of Modena and Reggio Emilia, Modena, Italy.
  • Bettelli S; Department of Diagnostic Medicine and Public Health, Section of Pathology, University of Modena and Reggio Emilia, Modena, Italy.
Dis Markers ; 2018: 2959801, 2018.
Article en En | MEDLINE | ID: mdl-30018674
ABSTRACT
Stage I colorectal carcinoma has excellent prognosis, with 5-year survival rate up to 95%. The occurrence of lymphovascular invasion, tumor budding, high number of PDC, or lymph node micrometastases is associated with tumor progression. The aim of this study was to evaluate the mutational status of 62 stage I colorectal carcinomas (CRC) (taken from 37 patients surviving more than five years since the initial diagnosis and from 25 patients who died of disease) and to correlate it with histopathological features and the clinical outcome. Mutations of KRAS, NRAS, BRAF, and PIK3CA genes were analyzed through Myriapod Colon Status Kit, using the high-throughput genotyping platform Sequenom MassARRAY System. Mutations in those genes were found in 31 cases (50%) and mainly in those with poor prognosis. The most frequent mutations occurred at codons 12 and 13 of the KRAS gene (40% of cases). We found concomitant PIK3CA mutations in 5 cases (8%). The presence of PIK3CA mutations was mainly observed in tumors with poor prognosis and with unfavorable histopathological prognostic features. High PDC grade (P = 0.0112), the presence of tumor budding (P = 0.0334), LVI (P < 0.0001), KRAS mutations (P = 0.0228), PIK3CA mutations (P = 0.0214), multiple genetic mutations in KRAS and PIK3CA genes (P = 0.039), and nodal micrometastases (P < 0.0001) were significant prognostic variables for CSS. The presence of LVI was the only independent and statistically significant prognostic variable for CSS in our cohort of pTNM stage I CRCs. The analysis of KRAS/PIK3CA mutational status may be used to identify patients with stage I CRC at high risk of bad outcome and who may need additional treatments, including biological therapies.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Carcinoma / Neoplasias Colorrectales / Biomarcadores de Tumor / Proteínas Proto-Oncogénicas p21(ras) / Proteínas Proto-Oncogénicas B-raf / Fosfatidilinositol 3-Quinasa Clase I / Mutación Tipo de estudio: Prognostic_studies Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Dis Markers Asunto de la revista: BIOQUIMICA Año: 2018 Tipo del documento: Article País de afiliación: Italia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Carcinoma / Neoplasias Colorrectales / Biomarcadores de Tumor / Proteínas Proto-Oncogénicas p21(ras) / Proteínas Proto-Oncogénicas B-raf / Fosfatidilinositol 3-Quinasa Clase I / Mutación Tipo de estudio: Prognostic_studies Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Dis Markers Asunto de la revista: BIOQUIMICA Año: 2018 Tipo del documento: Article País de afiliación: Italia