Piotr Wójcik

CDH1 gene promoter hypermethylation in gastric cancer - Relationship to Goseki grading, microsatellite instability status, and EBV invasion

Hypermethylation of the CDH1 promoter region seems to be the most common epigenetic mechanism in this gene silencing in gastric cancer. In this study, CDH1 promoter hypermethylation was observed in 54.8% (46/84) of the analyzed sporadic gastric carcinomas. We introduce a new relation: clustering of Goseki grading into 3 grade was determined by CDH1 promoter hypermethylation. The percentage of methylation in Goseki III cancers was significantly higher (83%) when compared with other grades; the lowest proportion was detected in IV (36%) and II (38%) groups, whereas grade I demonstrated typical percentage of promoter hypermethylation. A novel polymorphism R732R in exon 14 of the CDH1 gene was detected by mutational analysis. Additionally, all cases with the MSI-high phenotype revealed CDH1 promoter hypermethylation. In MSI-low and MSS gastric cancers, this percentage was lower, reaching 71% and 41%, respectively. Moreover, the methylation status was correlated with the LOH phenotype. We detected CDH1 promoter hypermethylation in all EBV-positive gastric cancers (5/5), whereas methylation in the EBV-negative group occurred in 58% of cases. We also report that “methylated” tumors were slightly larger than “nonmethylated,” whereas the second group revealed a higher probability of longer patient survival, though these relationships were not statistically significant. These results suggest that downregulation of E-cadherin, caused by promoter hypermethylation, in sporadic gastric carcinomas may be associated with a worse prognosis and specific tumor phenotype.

RAS mutation prevalence among patients with metastatic colorectal cancer: A meta-analysis of real-world data

Aim: A confirmed wild-type RAS tumor status is commonly required for prescribing anti-EGFR treatment for metastatic colorectal cancer. This noninterventional, observational research project estimated RAS mutation prevalence from real-world sources. Materials & methods: Aggregate RAS mutation data were collected from 12 sources in three regions. Each source was analyzed separately; pooled prevalence estimates were then derived from meta-analyses. Results: The pooled RAS mutation prevalence from 4431 tumor samples tested for RAS mutation status was estimated to be 43.6% (95% CI: 38.8–48.5%); ranging from 33.7% (95% CI: 28.4–39.3%) to 54.1% (95% CI: 51.7–56.5%) between sources. Conclusion: The RAS mutation prevalence estimates varied among sources. The reasons for this are not clear and highlight the need for further research.