Zlobec, Inti; Bihl, Michel P; Foerster, Anja; Rufle, Alex; Terracciano, Luigi; Lugli, Alessandro (2012). Stratification and Prognostic Relevance of Jass's Molecular Classification of Colorectal Cancer. Frontiers in oncology, 2, p. 7. Lausanne: Frontiers Research Foundation 10.3389/fonc.2012.00007
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Background: The current proposed model of colorectal tumorigenesis is based primarily on CpG island methylator phenotype (CIMP), microsatellite instability (MSI), KRAS, BRAF, and methylation status of 0-6-Methylguanine DNA Methyltransferase (MGMT) and classifies tumors into five subgroups. The aim of this study is to validate this molecular classification and test its prognostic relevance. Methods: Three hundred two patients were included in this study. Molecular analysis was performed for five CIMP-related promoters (CRABP1, MLH1, p16INK4a, CACNA1G, NEUROG1), MGMT, MSI, KRAS, and BRAF. Methylation in at least 4 promoters or in one to three promoters was considered CIMP-high and CIMP-low (CIMP-H/L), respectively. Results: CIMP-H, CIMP-L, and CIMP-negative were found in 7.1, 43, and 49.9% cases, respectively. One hundred twenty-three tumors (41%) could not be classified into any one of the proposed molecular subgroups, including 107 CIMP-L, 14 CIMP-H, and two CIMP-negative cases. The 10 year survival rate for CIMP-high patients [22.6% (95%CI: 7-43)] was significantly lower than for CIMP-L or CIMP-negative (p = 0.0295). Only the combined analysis of BRAF and CIMP (negative versus L/H) led to distinct prognostic subgroups. Conclusion: Although CIMP status has an effect on outcome, our results underline the need for standardized definitions of low- and high-level CIMP, which clearly hinders an effective prognostic and molecular classification of colorectal cancer.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute of Pathology |
UniBE Contributor: |
Zlobec, Inti, Lugli, Alessandro |
ISSN: |
2234-943X |
Publisher: |
Frontiers Research Foundation |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 14:32 |
Last Modified: |
05 Dec 2022 14:10 |
Publisher DOI: |
10.3389/fonc.2012.00007 |
PubMed ID: |
22655257 |
BORIS DOI: |
10.7892/boris.12502 |
URI: |
https://boris.unibe.ch/id/eprint/12502 (FactScience: 218854) |
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