Differences in Pathology and Mutation Status Among Colorectal Cancer Patients Younger Than, Older Than, and of Screening Age

Abstract

BackgroundScreening protocols for colorectal cancer are broadly recommended and effective in reducing mortality. However, populations from different age groups can harbor distinct pathologic and molecular profiles that can also be influenced by screening and polyp resection, especially in older ages. Patients and MethodsWe retrospectively analyzed tumors from stage IV colorectal cancer patients from a central pathology laboratory in Brazil that is a reference for mutational profiling countrywide. Patients were classified into age groups as follows: prescreening age (PrSA; < 45 years old), screening age (SA; 45-75 years old), and postscreening age (PoSA; > 75 years old). Every tumor was centrally reviewed by the pathologist. Groups were compared regarding clinicopathologic features, and the presence of RAS (renin–angiotensin system) and BRAF (v-Raf murine sarcoma viral oncogene homolog B) mutations. ResultsWe included 1635 patients (215 PrSA, 1213 SA, 207 PoSA). There was no difference among groups regarding sidedness (P = .65) and KRAS (Kirsten rat sarcoma viral oncogene) mutations (P = .57). Stage IV disease at diagnosis (P = .04), the presence of a signet-ring cell component (P < .001), and poorly differentiated tumors (P = .02) were most common in young patients, while BRAF and NRAS (neuroblastoma RAS viral (v-ras) oncogene homolog) mutations were significantly more common among PoSA patients (P = .002 and .03, respectively). When divided by age decade, KRAS mutations seem to have a stable frequency among all ages, while the BRAF mutation rate increased with increasing age. ConclusionBRAF mutations are more frequent among PoSA patients, and this seems to be a continuous trend. PrSA and PoSA patients seem to present a distinct profile from SA, including differences in molecular and pathologic aspects. These findings could impact the frequency of screening tests among different age groups.