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Clinicopathological and protein characterization of BRAF- and K-RAS-mutated colorectal cancer and implications for prognosis

Zlobec, Inti and Bihl, Michel P. and Schwarb, Heike and Terracciano, Luigi and Lugli, Alessandro. (2010) Clinicopathological and protein characterization of BRAF- and K-RAS-mutated colorectal cancer and implications for prognosis. International journal of cancer, Vol. 127, H. 2. pp. 367-380.

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Official URL: http://edoc.unibas.ch/dok/A6006153

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Abstract

Recent evidence highlights the potential prognostic and predictive value of BRAF and K-RAS gene alterations in patients with colorectal cancer. However, a comprehensive evaluation of BRAF and K-RAS mutations and their specific clinicopathological features, histomorphological presentation and effect on protein expression have not been systematically analyzed. The aim of this study was to characterize the clinicopathological, histomorphological and protein expression profiles of BRAF- and K-RAS-mutated colorectal cancers and determine their impact on patient survival. Molecular analysis for microsatellite instability (MSI), K-RAS and BRAF was carried out on paraffin-embedded samples from 404 patients with primary colorectal cancer. Using tissue microarrays, 36 tumor-associated and 14 lymphocyte/inflammatory-associated markers were evaluated by immunohistochemistry. BRAF mutation was associated with right-sided tumor location (p > 0.001), higher tumor grade (p = 0.029), absence of peritumoral lymphocytic inflammation (p = 0.026) and MSI-H (p > 0.001). In right-sided tumors, loss of CDX2 expression was observed in 23 of 24 cases (95.8%). BRAF mutation was a poor prognostic indicator in patients with right-sided disease (p = 0.01). This result was maintained in multivariable analysis (p > 0.001; HR = 2.82; 95% CI: 1.5-5.5) with pT, pN and vascular invasion and independent of CDX2 expression. K-RAS mutation, in contrast, was not associated with any of the features analyzed. BRAF gene mutation is an adverse prognostic factor in right-sided colon cancer patients independent of MSI status and, moreover, in patients with lymph node-negative disease. These results indicate that molecular analysis for BRAF may be a useful biomarker for identifying patients with right-sided colon cancer with poor outcome who may benefit from a more individualized course of therapy.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
UniBasel Contributors:Terracciano, Luigi M. and Lugli, Alessandro and Zlobec, Inti
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Alan R. Liss
ISSN:0020-7136
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:19 Jul 2013 07:43
Deposited On:19 Jul 2013 07:35

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