Colorectal Cancer Incidence, Location, Anatomy and Pathogenesis

Incidence and Location

The incidence of CRC increases with age and is highest during the eighth decade of life. Colorectal cancer has shown a gradual shift in location from left-sided to right-sided tumors over the past several decades. Rosato and Marks compared the distribution of CRC from 1939 to 1957 to that for a group of patients from 1970 to 1977. Percentages of cancers based on location for 1939 to 1957 and 1970 to 1977, respectively, have shifted as follows: rectum colon 51% versus 32%, sigmoid colon 13% versus 31%, descending colon 20% versus 5%, transverse colon 4% versus 13%, and ascending colon 12% versus 16%. In a prospective study, Tedesco et al. evaluated 642 patients and found that 66% of polyps and cancers were located within 60 cm of the anus, and that 5% of polyps and 28% of cancers were located within the first 25 cm. Knowledge of this shift from predominantly left-sided to right-sided tumors is an important consideration when discussing diagnostic studies.

Anatomy and Pathogenesis

The colon runs from the cecum to the rectum. Lymphatic drainage occurs in both a segmental and a circumferential fashion. This segmented drainage pattern explains why CRCs may appear as a localized, apple-core-type lesion. Histologically, normal colonic columnar epithelium is proliferative only in the lower two thirds of the glandular crypts. The upper one third and surface cells are normally nonproliferative. When exposed to carcinogens, mutational activation of oncogenes and the inactivation of tumor suppresser genes occur. At least four or five mutations are required to produce a malignant tumor. Cumulative mutations are responsible for the biologic properties of the tumor.

Exposure of normal colonic epithelium to carcinogens leads to the movement of proliferative cells from the basal two thirds of the crypts to the surface cell layer. These cells replicate but do not exfoliate, leading to increasing numbers of cells and eventual polyp formation. Polyps can be sessile (broad-based) or pedunculated (on a stalk), with the polyp’s histology being hyperplastic or neoplastic. If neoplastic, polyps are classified as adenomatous (tubular), villous (finger-like), or mixed (intermediate). Adenomatous polyps, if left untreated, may become progressively more dysplastic and eventually develop into carcinoma in situ or invasive CRC.

Gregory L. Brotzman and Russell G. Robertson


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