Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial.


Autoria(s): Roth Arnaud D.; Tejpar Sabine; Delorenzi Mauro; Yan Pu; Fiocca Roberto; Klingbiel Dirk; Dietrich Daniel; Biesmans Bart; Bodoky Gyoergy; Barone Carlo; Aranda Enrique; Nordlinger Bernard; Cisar Laura; Labianca Roberto; Cunningham David; Van Cutsem Eric; Bosman Fred
Data(s)

2010

Resumo

PURPOSE: Mutations within the KRAS proto-oncogene have predictive value but are of uncertain prognostic value in the treatment of advanced colorectal cancer. We took advantage of PETACC-3, an adjuvant trial with 3,278 patients with stage II to III colon cancer, to evaluate the prognostic value of KRAS and BRAF tumor mutation status in this setting. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded tissue blocks (n = 1,564) were prospectively collected and DNA was extracted from tissue sections from 1,404 cases. Planned analysis of KRAS exon 2 and BRAF exon 15 mutations was performed by allele-specific real-time polymerase chain reaction. Survival analyses were based on univariate and multivariate proportional hazard regression models. RESULTS: KRAS and BRAF tumor mutation rates were 37.0% and 7.9%, respectively, and were not significantly different according to tumor stage. In a multivariate analysis containing stage, tumor site, nodal status, sex, age, grade, and microsatellite instability (MSI) status, KRAS mutation was associated with grade (P = .0016), while BRAF mutation was significantly associated with female sex (P = .017), and highly significantly associated with right-sided tumors, older age, high grade, and MSI-high tumors (all P < 10(-4)). In univariate and multivariate analysis, KRAS mutations did not have a major prognostic value regarding relapse-free survival (RFS) or overall survival (OS). BRAF mutation was not prognostic for RFS, but was for OS, particularly in patients with MSI-low (MSI-L) and stable (MSI-S) tumors (hazard ratio, 2.2; 95% CI, 1.4 to 3.4; P = .0003). CONCLUSION: In stage II-III colon cancer, the KRAS mutation status does not have major prognostic value. BRAF is prognostic for OS in MS-L/S tumors.

Identificador

http://serval.unil.ch/?id=serval:BIB_B7EE37F01C41

isbn:1527-7755[electronic]

pmid:20008640

doi:10.1200/JCO.2009.23.3452

isiid:000273662700018

Idioma(s)

en

Fonte

Journal of Clinical Oncology, vol. 28, no. 3, pp. 466-474

Palavras-Chave #Metastatic Colorectal-Cancer; Kirsten Ras Mutations; K-RAS; Microsatellite Instability; Methylator Phenotype; Poor Survival; Metaanalysis; Carcinoma; Cetuximab; TP53
Tipo

info:eu-repo/semantics/article

article