What are Tumour Markers?
In medicine, a tumour refers to a growth in the body that results from uncontrolled cell division and can occur due to myriad reasons, including genetic mutations, environmental exposure, or as a result of ageing. A tumour may be either benign (non-cancerous) or malignant (cancer). Malignant tumours tend to be more aggressive and have the potential to spread to other parts of the body.
Tumour markers refer to substances produced in large quantities by cancer cells or in other cells in the body in response to the presence of a tumour. Tumour markers can provide information about a cancer, including how aggressive it is, and whether it can be treated with certain targeted therapies, and can also be used during the treatment process to track response to treatment.
Broadly speaking, common digestive tumour markers (gastrointestinal, liver, biliary tract and pancreatic cancers) include alpha fetoprotein (AFP), carcinoembryonic antigen (CEA) and CA 19-9)
Dr Benjamin Yip explains: “whilst tumour markers are not supposed to be done for screening purposes usually, it is commonly done as part of health screening packages.” If you are found to have a raised digestive tumour marker, it is prudent to discuss with your Gastroenterologist what to do next.
Carcinoembryonic Antigen (CEA)
CEA is a type of oncofetal antigen, i.e. a substance that is produced by tumours and also by foetal tissues, with much lower concentrations present in normal adult tissues such as the intestines, pancreas, and liver.
In general, mild to moderate elevations in CEA are found in those with benign diseases in the colon, pancreas, liver, as well as the lungs. These include diseases such as liver cirrhosis, hepatitis, pancreatitis, inflammatory bowel disease, bronchitis, pneumonia and autoimmune diseases. When the levels of CEA are markedly elevated and rise continuously in an exponential fashion, this may be associated with malignant cancers of the colon as well as metastatic cancers to the bone, liver, lung and lymph nodes.
In clinical practice, CEA is used primarily to track the response to treatment in those with colorectal cancer, and it is used to monitor for cancer remission as well as any potential relapse (i.e. when the CEA levels rise up again after recovery) after surgery.
In the general population, however, CEA is neither sensitive nor specific to be used as a general screening test for colorectal cancer. It would be more prudent to follow national guidelines such as doing a yearly faecal blood test for screening, e.g. faecal immunochemical test (FIT) or faecal occult blood testing (FOBT), or going for 5 to 10-yearly colonoscopies if you are above 50 years old.
Alpha Fetoprotein (AFP)
AFP is a glycoprotein that is formed in the foetus. It is present in the yolk sac of the foetal embryo, as well as in the liver and gastrointestinal tract of the foetus. It can be detected during the 4th week of pregnancy onwards, and its level peaks around weeks 12-15 before falling continuously until birth. By the age of 1, AFP levels in the body stabilise and stay at the same low concentration until adulthood.
AFP is useful for obstetrics as it can help to detect any foetal abnormalities and diseases in the foetus. In adults, AFP may be raised in benign liver diseases such as hepatitis, as well as in primary liver cancer, also known as hepatocellular carcinoma (HCC) and germ cell tumours. AFP may also be found in certain patients with metastatic breast, lung, and colorectal cancers that have spread to the liver.
In clinical practice, AFP is useful in helping to monitor treatment progress for HCC, and is usually done in conjunction with other tests to help diagnose HCC in high-risk groups, such as in those with chronic Hepatitis B infection, where a liver ultrasound and AFP blood test is sent every 6 months to check for the development of HCC.
Carbohydrate Antigen 19-9 (CA 19-9)
CA19-9 is a glycolipid found in foetuses that are produced in the lining, or epithelium of the stomach, intestine, and pancreas. In adults, CA19-9 exists in very low levels in the pancreas, liver and lungs, as well as many mucosal cells.
Because it is eliminated by bile, CA19-9 levels may be raised in cases where there is bile duct obstruction as bile cannot get released, which leads to CA19-9 levels building up in the body. CA19-9 may also be raised in cystic fibrosis (a genetic condition) and inflammatory bowel disease.
In terms of cancer management, CA19-9 is the cancer marker of choice for pancreatic cancers. High levels >1000U/ml suggest lymph node spread, and levels >10,000U/ml may indicate that the pancreatic cancer has spread to other parts of the body. CA19-9 is also associated with stomach cancer, although it is less sensitive and specific, and is not used as a screening.
What are Digestive Tumour Markers for?
The usefulness of clinical tumour markers and their use as a general screening tool is still under debate, although they may play a role in follow-ups of cancer treatment and to help detect relapse or further spread of cancer. Current-day research states that CEA is typically used for colon cancer follow-up, AFP for HCC detection and management, and CA19-9 for pancreatic cancer.
While there are many different tumour markers for different kinds of cancer, not all markers are specific for just one type of cancer and tumour markers may not necessarily always indicate the presence of cancer and may be associated with other non-cancerous health conditions as well. As such, while useful in cancer management, tumour markers should not be used on their own for cancer diagnosis as without proper interpretation, and further tests have to be conducted for a definitive diagnosis.
What does it mean to have raised Digestive Tumour Markers?
Raised tumour markers may indicate many things, including the formation of cancer in the body, cancer recurrence, or other medical issues. However, it is important to note that raised cancer markers are not a firm indicator for any diagnosis and other tests have to be done to formally diagnose a cancer. This includes taking a thorough medical history, physical examination, blood tests, imaging studies including x-rays and CT scans, and biopsies of tissue.
Cancer markers, when used as part of follow-up and monitoring during ongoing cancer treatment, can be useful in signifying either a cancer recurrence or that treatment is ineffective. This may signal to your doctor that there may be a need to use stronger medication, a different drug, or a different kind of treatment altogether.
Can stress cause Digestive Tumour Markers to rise?
Currently, there is no firm research done that shows an association between psychological stress and digestive tumour markers. However, certain benign, non-cancerous medical conditions may cause certain tumour markers to rise, such as CEA in pancreatitis, although the elevations tend to be transient and will resolve once the condition is cured.
What are the tests for Digestive Tumour Markers AFP, CEA and CA 19-9?
Tumour markers are tested by blood tests. Samples will be sent to a lab for testing, and the results will then be interpreted by your gastroenterologist.
When interpreted appropriately, tumour markers may be useful in helping detect your risk for certain conditions, and to help track the efficacy of treatment. Tumour markers must be used carefully and must be interpreted while also taking into account patients’ symptoms, clinical signs, and results of other investigations done during the care process.
- Mayer, RJ. “The use of serologic tumor markers in gastrointestinal malignancies.” PubMed, https://pubmed.ncbi.nlm.nih.gov/8707771/. Accessed 16 November 2022.
- “Tumor Markers in Common Use - NCI.” National Cancer Institute, 11 May 2021, https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-list. Accessed 16 November 2022.