Figure 9: Colorectal Intraepithelial Neoplasia (IEN). Within the epithelial
lining of the colon, a small adenomatous polyp is forming (A) following
some genetic damage. Over a period of time, loss of the tumor suppressor
gene APC within that same polyp, leads to an adenoma (B). Given more
time, this adenoma will acquire more genetic mutations, like the overactive
signaling pathways K-Ras and epidermal growth factor receptor (EGFR),
leading to the formation of a carcinoma in situ (C). The accumulation of
these changes leads to increasing levels of dysplasia, or changes in cell
shape, as the tumor continues to gain “independence” from normal cellular
and tissue-level controls. Prognosis at the carcinoma in situ stage is still
very good. Finally, after the accumulation of further genetic mutations, in
this case loss of the tumor suppressor gene p53, the tumor begins to
metastasize (D) into the nearby blood (BV) and lymphatic (L) vasculatures.
Routine colonoscopies are aimed at detecting and removing early stage
lesions like those in A and B.