P-0206 Early-Onset Colorectal Cancer: The Comparative Molecular Classification Suggests The Existence of Two new Different Groups Within Colorectal Cancer

Abstract

ABSTRACT Introduction Early-onset colorectal cancer (CRC) is an indicator of a hereditary component, but recently this is changing. The aim of our study was to compare the CRC molecular classification from the three main carcinogenetic pathways for two different populations, young and elderly, in order to identify any particular group in the early-onset population. Methods We analyzed a total of 119 CRC-patients from 2002 to 2008. Forty-five were early-onset CRC, and 74 older than 69. We analyzed the microsatellite instability (MSI) and CpG Islands Methylator Phenotype (CIMP) in both populations, classifying them into 4 main subtypes: MSI with CIMP-high (group A), MSI with CIMP low-0 (group B); Microsatellite Stability (MSS) with CIMP-high (group C), and MSS with CIMP low-0 (group D). We analyzed the clinic-pathological and familial differences between every group within each population and also each group between both populations. Only statistically significant differences are shown. Results Within early-onset CRC we observed that in group A, 100% of CRC were located in right colon versus group D, in which 90% of CRC were in left colon and rectum. In majority of groups tumours were mucinous, except in group D (89% were not). A 100% and 40% of CRC in group A and B were Lynch syndrome cases, whereas none within the other groups. The majority of early-onset CRC associated polyps. In group C, 100% were mixed polyps whereas in group D and A, 72% and 50% were adenomatous polyps, respectively. Familial cancer history in young CRC was frequent but different depending on the subtype. In group A and B 100% and 80% of the patients fulfilled Amsterdam II criteria; in group C and D, 57% and 52% had only familial aggregation for Lynch syndrome-related and unrelated cancers. Within elderly CRC population we observed that in group A and B, 67% and 100% of tumours were located in the right colon whereas in group C and D, 75% and 59% were in the left colon and rectum, respectively. Mlh1 expression were absent in 83% and 50% of cases in group A and B. Taking into account the comparison of each correlative group between both populations, no significant differences were found for groups A and B. For group C, 57% of early-onset CRC were right colon tumours compared with 75% of the elderly CRC (rectum). 100% of polyps within early-onset CRC were mixed vs 62.5% of adenomatous in the elderly. 43% of early-onset CRC had familial aggregation while all of the elderly were sporadic. For group D, 52% of young CRC were located in the left colon compared with 41% of right in the elderly. 46% of early-onset CRC showed familial aggregation whereas 83.6% of sporadic in the elderly. 51.6% and 32.3% of early-onset CRC had familial history for Lynch syndrome-related and unrelated cancers, respectively, compared with 32.3% and 10% of the elderly. Conclusion We identified two differential groups within early-onset CRC, with MSS, depending on the CIMP subtype, showing group C mainly anatomo-clinical differences, and group D familiar differences.