From Polyp to Cancer

Almost all colorectal cancer starts in the mucosa the inntermost lining of the large intestine. The intestines are made of five layers. Starting from the inside of the intestine or lumen (lumen refers to the empty space or cavity), the first layer is the mucosa where nutrients, fats and proteins are absorbed from the foods we eat (this is also the layer that is biopsied during a colonoscopy). Next is the muscularis mucosa that forms a barrier between the mucosa and the third layer called the submucosa. The submucosa is rich in vessels that provide the intestines with their blood supply while carrying the digested nutrients away to other vital organs. The fourth layer is the muscularis propria, which acts to propel food through the intestines, and the outermost layer is the serosa.

Cut away view of rectum and magnification of the various layers colonic tissue.

Colorectal cancers usually begin as benign polyps that grow from the mucosa. Some individuals are more likely than others to develop polyps, especially those with a personal or family history of polyps and/or colorectal cancer, and those that carry specific genes for hereditary forms of colorectal cancer. New information has also indicated that individuals who have type 2 diabetes and those who are considered obese are also at greater risk for developing polyps and colorectal cancer.

Most polyps remain benign and are often termed hyperplastic polyps. The likelihood that hyperplastic polyps will become cancer is very low. Other benign polyps are sometimes referred to as pre-cancerous.  These polyps are not malignant, themselves, but have a chance of becoming cancerous if not removed. Examples include adenomatous and hamartomatous polyps. Adenomatous polyps that have tubular or villous characteristics have a higher chance of becoming cancerous. Adenomatous and hamartomatous polyps are also the types of polyps that are usually associated with hereditary colorectal cancer syndromes. The only truly Òmalignant polypÓ is one that has been shown to contain invasive carcinoma. Sometimes the carcinoma is confined to the polyp, and other times it has invaded one or more layers of the intestine.

Adenomas usually grow on a stalk, resembling small mushrooms. They tend to grow slowly over a decade or more. The risk of an adenoma developing into cancer increases as the size of the adenoma increases and with the amount of time the have been growing in the colon. Adenomas that are malignant are called adenocarcinomas. In the very early stages, abnormal cells are contained inside the polyp and can be easily removed by colonscopy before the develop into invasive cancer. However, as cancer cells grow and divided within the polyp, they can eventually invade nearby colon tissue and grow into and beyond the wall of the colon or rectum. If the cancer becomes advanced, the tumors will grow though all of the tissue layers of the colon rectum, and may metastasize, shedding cells into the circulatory system, spreading the cancer to other organs such as the liver and lungs.

Progression from Polyp to Cancer

Fewer than 10% of all adenomas become cancerous, however, more than 95% of colorectal cancers develop from adenomas. Recent research has also shown that some polyps long considered to be benign may also become cancerous as well. For this reason, doctors will remove all polyps during a colonoscopy screening. Small polyps are easily and painlessly removed, as they are snared and severed with a retractable wire loop that is passed through the colonoscope. As well, very small polyps may be destroyed with an instrument that delivers heats the polyps, delivering a small burst of electrical current. Very large polyps may require surgery, whether they are benign or cancerous.

Abnormal cell growth and inflammation can be another precancerous condition of the colorectal tissue, and is known as dysplasia. The abnormal areas and inflammatory polyps will be biopsied and sent to a pathologist who will examine the tissue form malignant cells. If they are benign, as they often are, then no further treatment is necessary, though your doctor will recommend a routine colonoscopy schedule to keep track of the area of your colon that appears abnormal.

The Discovery and Science of the Polyp to Cancer Progression

Scientists at Johns Hopkins were the first to describe the progression of a polyp to a colorectal cancer. Dr. Bert Vogelstein discovered that colorectal polyps and colorectal cancer develops as a result of genetic mutations or other chemical modifications, causing inactivation or promotion of specific genes known as tumor suppressor and tumor promoter genes. The ÒVogelgramÓ shown below, depicts the specific molecular events as a polyp transitions to a cancer. This genetic model of the pathway of colorectal cancer results from chromosomal instability, and details some of the most common point mutations that occur in colorectal cancer related tumor suppressor genes, such as APC, P53, as well K-ras, a common tumor promoter gene.

Vogelgram detailing the molecular alterations in multiple genes that cause Colorectal Cancer to develop in well-defined stages within an individual cell

As the Vogelgram depicts, the adenoma is considered to be the precursor lesion to CRC, occurring rarely in individuals under 49 (1.7-3.5%), but becoming more prevalent later in life. In the 6th, 7th, and 8th decades of life the prevalence of adenomas has been estimated to occur at a rate of 10%. The dwell time of an early adenoma to its maturation into an advanced adenoma has been projected to be approximately 2-5 years. Similarly, the dwell time of an advanced adenoma has been estimated at 2-5 years, before it matures into an early cancer.

Next: Diagnosis