Stratification and Prognostic Relevance of Jass's Molecular Classification of Colorectal Cancer

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)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Zlobec, Inti and Lugli, Alessandro

ISSN:

2234-943X

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:32

Last Modified:

08 Jun 2016 10:30

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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