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Colorectal carcinoma (CRC) affects 4% of the population, and up to 30% of patients have a family history of the disease. Identified hereditary syndromes such as Lynch syndrome (hereditary nonpolyposis colorectal cancer, or HNPCC) and familial adenomatous polyposis (FAP) account for only 10% of patients (Liccardo, 2017); risk factors such as age, diet, and smoking, or diseases such as diabetes and chronic inflammatory bowel disease, have also been implicated in increasing CRC risk (Siegel, 2017).
Early detection and screening methods such as sigmoidoscopy, colonoscopy, or stool-based tests for fecal blood (guaiac) or mutations (FIT-DNA) can reduce CRC deaths by detecting cancers and removing polyps at early stages, but once the cancer develops, treatment is often surgical with chemotherapy. Newer targeted therapies include EGFR inhibitors to slow the growth of the cancer and VEGF inhibitors to prevent the formation of blood vessels necessary for tumor growth.
IHC is used to identify CRC in tumors of unknown primary. CRCs express the nuclear transcription factor CDX2, which is highly specific for intestinal epithelial cells, and Villin, which is specific to adenocarcinomas of the GI tract. GPA33 codes for a membranous protein expressed in the majority of colorectal tumors.