The Cancer Detection Project / Gastrointestinal Cancer:
Demonstration of Antibody Staining of Cancerous Tissue
Cancer of the gastrointestinal tract, particularly the stomach and large bowel, is the most commonly occurring form of internal malignancy. Currently, the average Australian has at least a 1-in-24 life time risk of developing cancer of the large bowel. As the early diagnosis of malignancy may improve the prognosis of cancer patients, the search for new effective means for the detection of gastrointestinal and other cancers forms the second major area of research at the Centre for Molecular Biology and Medicine. Our investigations over many years have led to the development (in association with Mabtech Ltd., an independent diagnostics company with close links to the Centre) of an important cancer diagnostic assay.
Cancer of the gastrointestinal tract arises when the systems that normally control the natural growth cycles of the cells of the tract wall are disrupted allowing some cells to grow and divide in an uncontrolled way. When these uncontrolled cells avoid the body’s defenses they can grow to form a tumor. If this tumor remains contained at its original site and does not invade the surrounding tissue, it would usually be considered benign; however, if it starts to invade it is called a cancer. If the disease is untreated, cells from this primary cancer may migrate (metastasize) to other parts of the body and form secondary cancers. The best outcomes for the cancer patient are achieved when the cancer is detected and treated at the earliest possible time in its development. Tumor markers are important tools in the detection of cancers.
Tumor markers are substances that are produced by cancers. They are normally not present, or present at very low levels in healthy people. These markers can indicate the presence of cancers and may also be used to monitor the progression of the disease. At present, tumor marker tests for cancers of the gastrointestinal tract, prostate, ovary, breast and several other tissues are available. However, most of these tumor marker tests have limitations. New improved diagnostic tests for the detection of cancer are constantly being sought in order to improve detection rates, particularly at the early stages of cancer.
Use of Tumor Marker tests:
As an example, a typical course of events for a patient where bowel cancer is suspected, is given below. The most common, currently used tumor marker test for bowel cancers is the test for CEA
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A patient with a bowel complaint, where cancer is suspected, may be tested for the CEA, and an increased level observed. |
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This would lead to further tests, possibly concluding with a definite diagnosis of a cancer. |
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The surgical removal, or radio- or chemo-therapy of the cancer might then follow. |
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In some cases, surgery would be followed by a course of radio- or chemo-therapy. |
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Testing for CEA is then used during this treatment to indicate its effectiveness by monitoring CEA levels. |
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Testing for CEA is often used at regular intervals for a number of years to monitor the patient for recurrence of the cancer. |
In this way, a single patient may have a number of tests for the one marker during the course of their treatment and long term recovery.
The Small Intestinal Mucin Antigen (SIMA) - A Powerful Tumor Marker:
A major breakthrough was made in the early 1980s by Centre scientists researching the biochemistry of mucins of the digestive tract. Mucins are glycoproteins (chemical combinations of complex carbohydrate and protein) that form mucous gels that coat the surfaces of the digestive tract. This gel acts to protect the surfaces in the digestive tract from damage and to facilitate the movement of food through the system. It was discovered that when a cancer forms in the stomach or large bowel, the mucin produced by the cancer tissue is different from that of the surrounding normal tissue and indeed corresponds to the mucin normally found in the small intestine. It was also found that these mucins (SIMA) could be found in the blood of cancer patients.
The cancer mucin (SIMA) was recognized as a potential tumor marker for stomach and large bowel cancers and monoclonal antibodies were produced to detect it. A monoclonal antibody reacts specifically with a small part of a large complex molecule such as a mucin. In the course of the initial work, a number of antibodies were produced at the Centre that react with different parts (antigens) of the same cancer mucin. Of the many antibodies which detect SIMA that were developed, one denoted SIMA-4D3 was recognized as having major clinical potential. SIMA-4D3 detects a mucin antigen in the blood of patients with cancers of the stomach or large intestine; this mucin antigen does not occur to any significant extent in the blood of cancer free individuals.