Colorectal cancer in the very young: a comparative study of tumor markers, pathology and survival in early onset and adult onset patients

Introduction: Colorectal cancer (CRC) diagnosed before age 30 years is a fatal disease whose biology remains poorly understood. To understand its pathogenesis, we compared molecular and clinical data in surgically treated early-age onset and adult onset patients. Materials and Methods: Clinical data and tumor tissue were collected retrospectively for 94 patients with early-age onset CRC (age <= 30 years) and compared to 275 adult CRC patients (age >= 50 years). Tumor morphology, microsatellite instability (MSI) and stability (MSS), KRAS and BRAF mutations, and mismatch repair (MMR) expression (MSH2, MLH1, MSH6, PMS2) were assessed. Results: Early-age CRC was distinguished from adult CRC by advanced stage presentation (P < 0.001), frequent high grade cancers (P < 0.001), and poor prognosis (P < 0.001). MSI was associated with favorable survival and MMR loss in both groups. Compared to adults, MSI in early-onset CRC was more prevalent (P < 0.01), not tightly linked to MLH1/PMS2 loss, and never associated with BRAFV600E mutations (P < 0.01). MSS/BRAFV600E genotype had poor prognosis and was more prevalent in early-age CRC (9% vs. 3%). Discussion: Specific genetic subtypes are found at different frequencies in early-age onset and adult onset CRC. Complete absence of the indolent MSI/BRAFV600E genotype and enrichment in the unfavorable MSS/BRAFV600E genotype help explain the poor prognosis of early onset CRC. (C) 2016 Published by Elsevier Inc.