Tumour markers are those substances that can normally be found in the body or their level may rise up due to the presence of a cancer. These substances are usually found in the blood or urine. They can be products of cancer cells or of the body in response to cancer. Most of these tumour markers are protein in nature.
The presence of these tumour markers doesn’t necessary means or is not usually enough to diagnose or rule out cancer.Most tumour markers can also be made by normal cells as well as by cancerous cells. Sometimes, non-cancerous conditions can also cause increase the level of some tumour markers to be higher than normal. Besides, not every cancer patient may have raised level of a tumour marker. For these reasons, only a handful of tumour markers are commonly used by most doctors.
Uses of Tumour markers
- Tumor markers are used in diagnosing cancer In most cases, cancer can only be diagnosed by a biopsy and tumour markers are usually not used to diagnose cancer. However tumour markers can be useful to determine if a cancer is likely in some patients. It can also help diagnose the origin of the cancer in patients presenting with advanced widespread disease.
- They are also used for screening and Early Detection of Cancer.Screening refers to a rap and easy way of looking for cancer in people who have no symptoms of the disease, while early detection is finding cancer at an early stage. Although tumour markers were first developed to test for cancer in people without symptoms, very few tumour markers have been found to be helpful in this way because most tumour markers have not been shown to detect cancer much earlier than they would have been found otherwise.
- They are used to assess how aggressive a cancer is likely to be or even how well it might respond to certain drugs.
- To monitor patients being treated for cancer. If the initially raised tumour marker level goes down with treatment, it is an indication that the treatment is working and is having a beneficial effect on the patient. On the other hand, if the marker level goes up, then the treatment is probably not working and change of treatment should be considered as soon as possible.
- Tumour Markers are also used to detect recurrent cancers after initial treatment. Some tumour markers can be useful once treatment has been completed and with no evidence of residual cancer left. These include Prostate Specific Antigen (for prostate cancer), HCG (for gestational trophoblastic tumours & germ cell tumours of ovaries & testicles), and CA 125 (for epithelial ovarian cancer).
The following are list of tumour markers used and their clinical significances
- Alpha-fetoprotein (AFP)
- This tumour marker is elevated in hepatocellular carcinoma of liver and is useful to monitor response to treatment.
- It is also elevated in certain testicular cancers (embryonal cell & endodermal sinus types).
- An AFP level of less than 10 ng/mL is normal for adults. but an extremely high level ofAFP in your blood that is greater than 500 ng/mL—could be a sign of liver tumors.
2.Bladder tumour antigen (BTA)
- Bladder Tumour Antigen commonly found in urine of many patients suffering from bladder cancer.
- BTA test results are reported qualitatively as either positive or negative.
It can be used together with NMP22 (nuclear matrix protein) to detect recurrent tumour of the bladder.
- The test is not widely used and is still being studied.
- It is not certain whether it is as sensitive as cystoscopy for diagnosis & follow-up.
3.Beta-2 microglobulin (B2M)
- Elevated B2M is found in multiple myeloma, chronic lymphocytic leukaemia (CLL) and some lymphomas.
- Patients with higher levels of B2M usually have a worse prognosis.
- B2M is often elevated in chronic renal failure and dialysis patients without cancer
4.Carcinoembryonic antigen (CEA)
- CEA is the best tumour marker used to monitor patients with colorectal cancer during treatment, not useful as a screening or diagnostic test.
- The higher the CEA level at time of diagnosis, the more likely it is that the disease is advanced.
- This marker can also be raised in cancer of lung, breast, thyroid, pancreas, liver, stomach, ovary and bladder.
- CEA can also be elevated in non-cancerous diseases and in chronic smokers.
5. Chromogranin A (CgA)
- The blood level of CgA is raised in patients with neuroendocrine tumours such as carcinoid tumours, small cell lung cancer,neuroblastoma and some rare cases of prostate cancer that have neuroendocrine features.
- CgA is probably the most sensitive tumour marker for carcinoid tumours: level raised in 1/3 of patients with localized disease and 2/3 with metastatic disease.
6. HER2 (Human Epidermal Growth Factor receptor or EGFR 2)
- About 25% of patients with breast cancer have tumours that overexpress HER2, which is associated with aggressive disease, poor clinical outcomes and shortened overall survival.
- Samples of tumour tissue (not blood sample) are used to test for HER2 status.
7. Estrogen / Progesterone receptors
- Breast tumour samples (not blood samples) from patients with breast cancer are tested for Estrogen
8. Human chorionic gonadotropin (HCG sometimes beta-HCG)
- Normally found in men and women but HCG blood levels are elevated in patients with some types of testicular & ovarian cancers (germ cell tumours), gestational trophoblastic disease, (mainly choriocarcinoma), mediastinal germ cell tumour.
- Serum HCG level can be used to help diagnose these tumours, monitor response to treatment and detect recurrence
- They are not really tumour markers but antibodies produced by immune system.
- Patients with myeloma or macroglobulinemia classically have a very high level of one specific (monoclonal) immunoglobulin.
10. Lipid associated sialic acid in (LASA-P)
- This marker has been studied as a marker for ovarian and some other cancers.
- it is not specific for any particular cancer or even for cancer in general, as it can be raised in some non-cancerous conditions hence was replaced by other more specific tumour markers.
11. Neuron -specific enolase (NSE)
- NSE, like Chromogranin (CgA), is another tumour marker for neuroendocrine tumours such as small cell lung cancer, neuroblastoma and carcinoid tumours.
- It is more useful in follow-up of patients with small cell lung cancer or neuroblastoma, while CgA seems to be a better marker for carcinoid tumours
- It is not used as a screening test.
- An elevated level can also be found in some non-neuroendocrine cancers.
12. NMP22 (Nuclear matrix protein)
- nuclear matrix protein is a protein found in nucleus of cells.
- Its Levels are often raised in urine of patients with bladder cancer.
- So far, it has not been shown to be sensitive enough for screening purpose
- It can be used to look for recurrence after treatment, but it is not sure whether NMP 22 monitoring is as accurate as cystoscopy and thus is not widely used.
- S-100 is a protein mostly found in melanoma cells.
- These tissue samples of suspected melanoma are often tested for this marker in order to aid diagnosis.
- Some studies have shown that blood levels of S-100 are raised in most patients with metastatic melanoma.
- Therefore, this test is sometimes used to look or follow up the spread of melanoma before, during or after treatment.
- TA-90 is another protein found on surface of melanoma cells.
- Similar to S-100, serum level of TA-90 can also be used to look for spread of melanoma.
- The role of TA-90 in monitoring melanoma is still being studied and it is not widely used at present.
- This protein is made by thyroid gland.
- It’s levels are raised in many thyroid diseases including some common forms of thyroid cancer.
- After complete & successful treatment of these thyroid cancer, serum thyroglobulin level should normally fall to undetectable levels but there is a subsequent rise,this may suggest that the tumour is recurring
- In patients with metastatic thyroid cancer, thyroglobulin levels can be used to evaluate the results of treatment over time.
16. Tissue polypeptide antigen (TPA)
- Tissue polypeptide antigen (TPA) is a protein tumour marker that is present in high levels in many rapidly dividing cells (including cancer cells).
- A TPA blood test is sometimes used together with other tumour markers to help follow up patients being treated for lung, bladder and many cancers.
- TPA levels are also raised in some non-cancerous conditions.
Prostate Tumour Markers
17. Prostate-specific antigen (PSA)
- PSA is another tumour marker use for the screening of prostate cancer.
- The PSA level can also be raised in some patients with benign prostatic hyperplasia, elderly men and those with larger prostates.
18. Prostatic acid phosphatase (PAP)
- It is another test for prostate cancer which was used before PSA test was developed.
- It is less sensitive as compared to PSA hence rarely used to screen for prostate cancer
19. Prostate-specific membrane antigen (PSMA)
- This PSMA is a substance normally found in all prostate cells.
- The Blood levels always increase with age and with prostate cancer.
- Therefore,PSMA is a very sensitive tumour marker, but so far it has not been proven to be better than Prostate Specific Antigen (PSA).
- PSMA current use is limited to being part of a nuclear scan to look for spread of prostate cancer in the body.
20. Prostate cancer antigen 3 gene (PCA 3)
- PCA 3 also known as Prostate Cancer Antigen 3 gene is a new gene-based test carried out on suspected patient urine sample.
- This tumour marker is highly specific to Prostate cancer and in contrast to PSA, is not increased by conditions such as benign enlargement or inflammation of the prostate.
- PCA3 gene testing holds potential in men with elevated Prostate Specific Antigent levels but no cancer on initial biopsy.
- Also PCA3 urine test can provide additional information that can help to decide whether a new biopsy is really needed or not
- The probability of a positive repeat biopsy increases with rising PCA3 level that is the higher the PCA3 level, the greater was the probability of a positive repeat biopsy.