Liver metastases from colorectal cancer remain a substantial problem. More effective treatments and mass screening represent promising approaches to decrease this problem.

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EUROCARE-3 analysed the survival of 1815584 adult cancer patients diagnosed from 1990 to 1994 in 22 European countries. The results are reported in tables, one per cancer site, coded according to the International Classification of Diseases (ICD)-9 classification. The main findings of the tables are summarised and commented on in this article. For most solid cancers, wide differences in survival between different European populations were found, as also reported by EUROCARE-1 and EUROCARE-2, despite a remarkable (10%) overall increase in cancer survival from 1985 to 1994. Survival was highest in northern Europe (Sweden, Norway, Finland and Iceland), and fairly good in central-southern Europe (France, Switzerland, Austria and Spain). Survival was particularly low in eastern Europe, low in Denmark and the UK, and fairly low in Portugal and Malta. The mix of tumour stage at diagnosis explains much of the survival differences for cancers of the digestive tract, female reproductive system, breast, thyroid, and also skin melanoma. For tumours of the urinary tract and prostate, the differences were explained mainly by differences in diagnostic criteria and procedures. The case mix by anatomic subsite largely explains differences in survival for head and neck cancers. For oesophagus, pancreas, liver and brain cancer, with poor prognoses, survival differences were limited. Tumours, for which highly effective treatments are available, such as testicular cancer, Hodgkin's lymphoma and some haematological malignancies, had fairly uniform survival across Europe. Survival for all tumours combined (an indicator of the overall cancer care performance of a nation's health system) was better in young than old patients, and better in women than men. The affluence of countries influenced overall cancer survival through the availability of adequate diagnostic and treatment procedures, and screening programmes.

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The RAS-MAPK, PI (3)K signaling pathways form a network that play a central role in tumorigenesis. The BRAF, KRAS and PI3KCA genes code 3 partners of this network and have been found to be activated by mutation in colorectal cancer; these mutations lead to unrestricted cell growth. We evaluated the clinicopathological features and the prognosis of patients with activated-network colon cancers in a population-based study. A total of 586 colon adenocarcinomas were evaluated using sequencing for mutations of KRAS and PI3KCA, and allelic discrimination for mutation of BRAF. Clinicopathological characteristics were correlated to the risk of bearing a mutation of the network using logistic regression. Three-year survival rates were compared with the Log rank test. A multivariate survival analysis using the Cox model was performed. After adjustment for age and microsatellite instability, activation of the network by mutation of at least 1 of the 3 genes was significantly associated with female sex (p 5 0.02) and proximal location (p < 0.001). Lower levels of 3-year survival were associated with activation of the network by mutation of at least 1 of the 3 genes (59.4 and 69.4%, respectively; p 5 0.009). These results remained significant in a multivariate analysis adjusted for sex, age, location, stage and microsatellite instability (HR 5 1.48; CI CI 95% 5 [1.07-2.04]). Our study is the first report to underline the potential role of RAS-MAPK, PI (3)K network mutations on survival in colon cancers. Because of the role of this signaling network on anticancer agents, the evaluation of its mutations could have clinical implications.

The CpG island methylator phenotype (CIMP) is a distinct phenotype in colorectal cancer, associated with specific clinical, pathologic, and molecular features. However, most of the studies stratified methylation according to two subgroups (CIMP-High versus No-CIMP/CIMP-Low). In our study, we defined three different subgroups of methylation (No-CIMP, CIMP-Low, and CIMP-High) and evaluated the prognostic significance of methylation status on a populationbased series of sporadic colon cancers. A total of 582 colon adenocarcinomas were evaluated using methylation-specific PCR for 5 markers (hMLH1, P16, MINT1, MINT2, and MINT31). No-CIMP status was defined as no methylated locus, CIMPLow status as one to three methylated loci, and CIMP-High status as four or five methylated loci. Clinicopathologic and molecular characteristics were correlated to the methylation status. Crude and relative survival was compared according to methylation status. In the microsatellite-stable (MSS) group, CIMP-High was significantly associated with proximal location (P = 0.011) and BRAF mutation (P < 0.001). KRAS mutations were more associated with CIMP-High and CIMPLow status (P = 0.008). A shorter 5-year survival was observed in MSS cancer patients with CIMP-Low or CIMP-High status. These results remained significant in multivariate analysis adjusted for age, stage, and BRAF and KRAS mutational status [CIMP-Low: hazard ratio (HR), 1.85; 95% confidence interval (95% CI), 1.37-2.51; CIMP-High, HR, 2.90; 95% CI, 1.53-5.49 compared with No-CIMP]. Within the high-level microsatellite instability group, no difference in survival was observed between the different CIMP groups. Our results show the interest of defining three subgroups of patients according to their methylation status (No-CIMP/CIMP-Low/CIMP-High). Methylation is an independent prognostic factor in MSS colon cancer. [Cancer Res 2008;68(20):8541-6]