Cimp-Positive Status is More Representative in Multiple Colorectal Cancers than in Unique Primary Colorectal Cancers

We thank the Tumor Registry of the Pathology Department of the 12 de Octubre University Hospital for providing the paraffin-embedded tissues, and Ron Hartong for his help with the English revision of this manuscript. This work was funded by Projects PI10/00683 and PI16/01650 to J.P, and PI16/01920 to R.G.S, from the Spanish Ministry of Health and Consumer Affairs and FEDER, and by Project 2012-0036 from the Mutua Madrileña Foundation. This work was supported by R01 (CA72851, CA181572, CA184792, CA202797) and U01 (CA187956, CA214254) grants from the National Cancer Institute, NIH; RP140784 from the CancerPrevention Research Institute of Texas; grants from the Baylor Foundation and Baylor Scott & White Research Institute, Dallas, TX, USA to AG.Colorectal cancer (CRC) with CpG island methylator phenotype (CIMP) is recognized as a subgroup of CRC that shows association with particular genetic defects and patient outcomes. We analyzed CIMP status of 229 individuals with CRC using an eight-marker panel (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1); CIMP-(+) tumors were defined as having ≥ 5 methylated markers. Patients were divided into individuals who developed a "unique" CRC, which were subclassified into early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and patients with multiple primary CRCs subclassified into synchronous CRC (SCRC) and metachronous CRC (MCRC). We found 9 (15.2%) CIMP-(+) EOCRC patients related with the proximal colon (p = 0.008), and 19 (26.8%) CIMP-(+) LOCRC patients associated with tumor differentiation (p = 0.045), MSI status (p = 0.021) and BRAF mutation (p = 0.001). Thirty-five (64.8%) SCRC patients had at least one CIMP-(+) tumor and 20 (44.4%) MCRC patients presented their first tumor as CIMP-(+). Thirty-nine (72.2%) SCRC patients showed concordant CIMP status in their simultaneous tumors. The differences in CIMP-(+) frequency between groups may reflect the importance of taking into account several criteria for the development of multiple primary neoplasms. Additionally, the concordance between synchronous tumors suggests CIMP status is generally maintained in SCRC patients.S