cancer tumour markers

A Complete Guide To Tumour and Cancer Markers

Learn everything about tumor and cancer markers, what they are used for, whether you need them, and where you can get a cancer marker test completed in Singapore.

by Samantha Poh

Early intervention is probably the most influential element in the prevention and treatment of tumour growth and cancers. Through the use of markers, we can quickly and easily obtain important preliminary information to detect tumours and treat them before they cause significant harm to a patient. 

Today, rapid advancements in medical science have identified a multitude of markers and are uncovering more, not just for the early detection of tumours, but also as key methods for analyzing different types of tumours, selecting suitable treatments, and monitoring cancer recovery.

What Are Tumour and Cancer Markers?

Tumours are formed by cancer cells, which are cells that have acquired defects, or mutations, in their genetic code and are proliferating uncontrollably as a result. Severe tumours that are growing rapidly and causing harm to nearby tissues and organs are classified as cancerous, while slow-growing tumours, which are usually small and not causing significant damage, are known as benign tumours. Markers may be specific to these different types of cancer cells, tumours, and cancers, but can be collectively referred to as tumour markers.

Most tumour markers are substances produced by cancer cells or other cells in response to the presence of a tumour and can be detected in a section of the tumour (biopsy), bodily fluids, or stools of the patient. These substances include:

  • Antigens
  • Antibodies
  • Other proteins & complexes
  • Hormones
  • Tumour tissue (biopsy)
  • Circulating cancer cells (liquid biopsy)

More recently, genomic markers that are characteristic of cancer cells have also been increasingly leveraged upon as powerful tumour markers. Genomic markers are:

  • Mutations in genetic codes
  • Changes in gene expression
  • Other changes in DNA
  • Messenger RNA (mRNA)

How Are Tumour Markers Used?

Tumour markers are used (often together with results from other tests such as imaging) for the following purposes:

  • Detect tumours & cancers (cancer screening)
  • Determine the type of cancer
  • Gauge cancer prognosis
  • Select the type of treatment
  • Monitor treatment effectiveness
  • Check for residual or recurrent tumours after treatment

Different tumour markers provide different types of information, and can be broadly divided into two groups, tumour tissue markers and circulating tumour markers.

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Tumour Tissue Markers

Tumour tissue markers, or tumour cell markers, are found in tumour tissue samples obtained through a surgical resection of the tumour itself (biopsy) or shedded tumours cells in blood samples (liquid biopsy). These tumour tissue markers are normally used for the diagnosis and evaluation of the type, stage, and prognosis of cancer. 

Additionally, tumour tissue markers provide critical insights for the selection of cancer treatment strategies. DNA extracted from the tumour tissue sample undergoes genomic analyses to identify biomarkers, or unique sequences of DNA, which reveals more about the cancer-causing mechanism and is used to assess the patient’s suitability for various targeted therapies.

For example, PROGRAMMED DEATH LIGAND 1 (PD-L1) is a protein that is erroneously over-produced in many types of cancer cells and prevents the natural immune response that eradicates cancer cells, allowing them to grow and divide uncontrollably. Through genomic analysis of the tumour DNA sample, this overexpression of PD-L1 is detected and is a biomarker which informs doctors that the appropriate treatment for the cancer is the use of immune checkpoint inhibitors targeting the PD-L1 mechanism.

Circulating Tumour Markers

Circulating tumour markers, which are substances found in samples of bodily fluids, such as blood and urine, are easily obtained from the patient and can be regularly analyzed without causing much discomfort nor inconvenience, making them potential markers for cancer screening. Generally, higher levels of these tumour markers are associated with more severe tumour progression but must be coupled with other tests, such as biopsies and imaging, to accurately diagnose and evaluate tumours. Tumour marker levels can also be logged periodically to estimate prognosis, assess the effectiveness of cancer treatment, and detect tumour recurrence.

An example of a commonly examined circulating tumour marker is CANCER ANTIGEN 125 (CA125), which is  a part of a protein known as MUC16, which promotes cancer cell proliferation and inhibits cancer-killing immune responses. As an increase in CA125 is often observed in existing ovarian cancer patients, long-term monitoring of CA125 levels in the blood is used as an ovarian cancer screening marker in the Risk of Ovarian Cancer Algorithm (ROCA). CA125 levels are also useful in gauging treatment response and checking for cancer recurrence in ovarian epithelial cancer and some other cancers.

Who Needs Tumour Marker Tests?

Anyone can take a tumour marker test. In particular, people at higher risk of cancers, people with benign tumours, cancer patients, and recovered cancer patients, are more inclined to undergo tumour marker tests. 

The risk of cancers increases with:

  • Age
  • Smoking
  • History of cancer in the family

If you are at high risk of cancer, your doctor may recommend cancer screenings which can involve tumour marker tests. In Singapore, the Ministry of Health (MOH) advises women aged 25 to 29 years old to take the pap smear test, while women aged 30 and above should take the human papillomavirus (HPV) test for cervical cancer screening every 3 years and 5 years respectively. Likewise, men aged above 50 years old are recommended to take the Prostate-Specific Antigen (PSA) test for prostate cancer screening annually.

Types of Tumour Marker Tests

Circulating tumour marker tests are conducted with samples of bodily fluids or excrements, including:

  • Cheek swab test
  • Blood test
  • Urine test
  • Stool test
  • Cerebrospinal fluid test
  • Liquid biopsy

Tumour tissue marker tests involve the removal of body or tumour tissue through a surgical procedure, known as a biopsy. These tests include:

  • Bone marrow biopsy
  • Tumour biopsy

Different types of cancers involve the use of different markers for various purposes, such as cancer severity, selecting treatments, and assessing treatment effectiveness and recurrence. A list of markers and their corresponding testing methods for various cancers are provided in the table below.

Type of CancerType of TestTumour Markers Detected
Stomach CancerTumour Biopsy- HER2/neu expression
- PD-L1 expression

Pancreatic CancerTumour Biopsy- HER2/neu expression
Blood Test- CA19-9 levels
- DPD gene mutation
Colorectal CancerTumour Biopsy- KRAS gene mutation
- MSI expression
- dMMR expression
- BRAF V600 mutation
Blood Test- Carcinoembryonic antigen (CEA)
- DPD gene mutation
Liquid Biopsy- Circulating tumor cells of epithelial origin (CELLSEARCH)
Ovarian CancerTumour Biopsy- HER2/neu expression
- BRCA1 & BRCA2 gene mutations
Blood Test- CA-125 levels
- HE4 levels
- OVA1 levels
Prostate CancerTumour Biopsy- 17-Gene signature
(Oncotype DX GPS test)
- 46-Gene signature (Prolaris)
Blood Test- Prostatic Acid Phosphatase (PAP) levels
- Prostate-specific antigen (PSA)
Liquid Biopsy- Circulating tumor cells of epithelial origin (CELLSEARCH)
Urine Test- PCA3 mRNA
Bladder CancerTumour Biopsy- HER2/neu expression
- FGFR2 & FGFR3 gene mutations
Urine Test- Bladder Tumor Antigen (BTA) levels
- Fibrin or fibrinogen levels
- Nuclear matrix protein 22 levels
Breast CancerTumour Biopsy- HER2/neu expression
- BRCA1 & BRCA2 gene mutations
- Estrogen & progesterone receptor characteristics
- Urokinase plasminogen activator (uPA)
- Plasminogen activator inhibitor (PAI-1
- 21-Gene signature (Oncotype DX
- 70-Gene signature (Mammaprint)
Blood Test- CA15-3 levels
- CA27.29 levels
- DPD gene mutation
Liquid Biopsy- Circulating tumor cells of epithelial origin (CELLSEARCH)
Lung CancerTumour Biopsy- PD-L1 expression
- BRAF V600 mutation
- EGFR gene mutation
- KRAS gene mutation
- ROS1 gene rearrangement
- ALK gene rearrangements & expression
Blood Test- Cytokeratin fragment 21-1 levels
- Neuron-specific enolase (NSE) levels
Lymphomas & LeukemiasTumour Biopsy- PD-L1 expression
- ALK gene rearrangement & expression
- Cyclin D1 (CCND1) gene rearrangement & expression
- RF4 gene rearrangement
- MYC gene expression
- MYD88 gene mutation
Blood Test- Chromosome 17p deletion levels
- Lactate dehydrogenase levels
- Terminal transferase (TdT) levels
Cheek Swab or Blood Test- Thiopurine S-methyltransferase (TPMT) enzyme activity or genetic test
Tumour Biopsy, Bone Marrow Biopsy or Blood Test- B-cell immunoglobulin gene rearrangement
- BCL2 gene rearrangement
- BCR-ABL fusion gene
- CD19, CD20, CD22, CD25, CD30, & CD33 levels
- T-cell receptor gene rearrangement
Blood, Urine, or Cerebrospinal Fluid Test- Beta-2-microglobulin (B2M) levels

What Happens During a Tumour Marker Test?

If you are undergoing a tumour marker test as part of a health screening, your doctor will first ask about your family medical history to deduce if you have any hereditary risk for certain types of cancers. They will then obtain a body fluid sample, usually a blood or urine sample, and send it to designated laboratories where tests for various diagnostic markers will be conducted.

If you have a tumour, your doctor may require a tumour marker test to aid in determining whether it is cancerous, its severity, and the disease prognosis. A tumour biopsy, where you will undergo tumour resection surgery, is often the most direct and reliable method in diagnosing a tumour. However, if the doctor decides that surgery is not required, or if the patient is unfit for surgery, a body fluid sample, such as blood, urine, or a swab sample, may be used for tumour marker tests instead.

If you are undergoing or have undergone treatment for a tumour or cancer, tumour marker tests may be required periodically to monitor treatment efficacy or to check if the tumour has recurred. A body fluid or swab sample will be taken periodically and sent for laboratory testing to track the levels of relevant circulating tumour markers in your body. Your doctor will then use the long-term data to assess whether the treatment is successful in regressing the tumour or if you are completely recovered without any signs of tumour recurrence.

Results from several tests for different tumour markers will be considered along with imaging tests, such as a magnetic resonance imaging (MRI) scan, and other tests, to make a reliable and comprehensive assessment of your tumour or cancer.

Limitations of Tumour Marker Tests

A tumour marker test does not provide conclusive results on its own. As its name suggests, tumour markers are indications of tumours and their characteristics, but these indications may vary naturally between individuals. Also, most circulating tumour markers are not directly associated with the tumour and are substances that are usually observed to be produced by the human body in response to a tumour. Yet, everyone’s immune system and other body systems react differently and may produce different amounts of tumour markers even if they have the same type of tumour. Furthermore, the levels of circulating tumour markers can be influenced by other unrelated conditions and diseases such as pregnancy, menopause, inflammation, or previous surgical removal of certain organs or tissues. 

As a result of these limitations, tumour marker tests can lead to erroneous conclusions such as:

  • Signifying the presence of a tumour when there is none, and vice versa
  • Showing that treatment is working when it is not, and vice versa

To overcome these limitations, some strategies are used when conducting and reading tumour marker test results:

Results Are Compared to a Range of Values

Results of the tumour marker tests are compared to a range of values. This values are based on large-scale assessments of healthy individuals and cancer patients,  and is known as the cancer marker range, to tolerate natural variation amongst individuals. If a person suspected to have a tumour has tumour marker levels which lie significantly outside of the healthy range, it is more likely that a tumour is actually present or aggressive.

Tumour Tissue Marker Test

If a tumour biopsy is possible, a tumour tissue marker test will be conducted as these markers are generally more robust and informative compared to circulating marker tests in telling us about the underlying mutation and mechanism that caused healthy cells to develop into cancer cells, and how to combat them. 

Multiple Tumour Markers Are Assessed Simultaneously

The results of these are collectively tabulated to give a probability or risk score. Multiple different tests are also conducted to ensure that their scores and conclusions are agreeable. For example, a tumour tissue marker test for prostate cancer patients, known as Prolaris, considers the gene expression signatures of 46 genes to give a final score ranging from 0 to 10. Doctors will use this score to determine the aggressiveness of the tumour and 10-year mortality risk. The scores from other prostate-cancer related tests, such as PSA and Gleason scores, may also be considered together to give an even more accurate disease prognosis.

Tumour Marker Tests Accompanied by Other Tests

Tumour marker tests are accompanied by other tests such as imaging tests to ensure that results from the various tests agree and come to a reliable conclusion.

Research regarding tumour markers is still actively ongoing. Powerful and reliable tumour markers may have yet to be discovered for the detection of some cancers, especially for cancer screening. In such cases, other cancer screening methods which rely chiefly on imaging tests rather than tumour markers are used, such as a mammogram, which uses X-ray imaging methods to detect tumours in early stage breast cancer screening, and colonoscopy for colorectal cancer screening.

Cancer Support Group & Resources

The battle against cancer can be a tiring, overwhelming, and lonely one. You may wish to reach out to cancer support groups to seek guidance, gain insights, and to share your experience with others that are fighting alongside you. 

If you are taking care of a cancer patient, it is important to take note of caregiving stress to ensure that you can continue to provide the best care and support for your loved one. In the unfortunate event of a terminal cancer diagnosis, you can still provide a fulfilling and high quality of life for your loved one through proper palliative care.

Homage is always available to provide tailored and professional care for cancer patients and also provides caregiving services for your loved ones at every stage. Our trained care professionals are able to provide companionship, nursing care, night caregiving, home therapy and more, to keep your loved ones active and engaged. 

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References
  1. National Cancer Institute. (2021, May 11). Tumor Markers. https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet
  2. National Cancer Institute. (2021, March 24). Biomarker Testing for Cancer Treatment. https://www.cancer.gov/about-cancer/treatment/types/biomarker-testing-cancer-treatment
  3. National Cancer Institute. (2021, May 11). Tumor Markers in Common Use. https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-list
  4. Ministry of Health. (2019). MOH Circular No. 08/2019: Release of new screening test review committee guidelines, including changes to diabetes mellitus, lipid disorders, and cervical cancer screening (MH 53:34/13). https://www.moh.gov.sg/docs/librariesprovider5/licensing-terms-and-conditions/moh-cir-no-08_2019_6mar19_screening.pdf
  5. Zak, K. M., Grudnik, P., Guzik, K., Zieba, B. J., Musielak, B., Dömling, A., … & Holak, T. A. (2016). Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1). Oncotarget, 7(21), 30323.
  6. Felder, M., Kapur, A., Gonzalez-Bosquet, J., Horibata, S., Heintz, J., Albrecht, R., … & Patankar, M. S. (2014). MUC16 (CA125): tumor biomarker to cancer therapy, a work in progress. Molecular cancer, 13(1), 1-15.
About the Writer
Samantha Poh
Samantha is an avid environmentalist pursuing her Ph.D. in biology. She promotes better management of nature, agriculture, and diets to empower both human and environmental health. To escape the fracas of deadlines and global issues, she explores the wondrous natural environments around the world and returns with newfound inspiration.
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