Unique clinicopathologic and genetic alteration features in early onset colorectal carcinoma compared with age-related colorectal carcinoma: a large cohort next generation sequence analysis.

Colorectal carcinoma (CRC) is the third most common cancer type in the United States. While the incidence of CRC is decreasing among an older population undergoing screening, the incidence of early-onset CRC is rising. There is a growing understanding that the molecular underpinnings of colorectal carcinoma vary by age. In this study, we report the genetic alterations and clinicopathologic features of a single-institution colorectal carcinoma cohort over a 2-year period using a next-generation sequencing (NGS) approach and microsatellite stability (MS) status determined by immunohistochemical staining. Forty cases were identified in an early-onset colorectal carcinoma cohort (eCRC) defined by age <40 years, and 164 cases were identified in an age-related colorectal carcinoma cohort (arCRC) defined by age >70 years. eCRC was more often-left-sided/rectal and more likely to present high rates of lymph node positivity with metastatic disease. NGS mutational analysis revealed distinct differences between eCRC and arCRC, with eCRC being characterized by low frequency of PIK3CA mutations, elevated frequency of KRAS and CTNNB1 mutations in microsatellite instability high tumors, and very low frequency of BRAF mutations.