Tumour marker
A tumour marker, also called a cancer biomarker, is a substance found in the body which concentration in the blood or other body fluid increases when cancer is present. The tumour marker may be produced by the cancer cells themselves or by healthy cells in response to the cancer. Tumour markers are usually proteins and are often produced in small amounts even in people without cancer. The term tumour marker may also be used to mean typical molecular changes in cancers, like ALK rearrangement and overexpression in NSCLC.
Tumour markers are not used for diagnosis of cancer, as they are not specific (can be elevated even without cancer) and are not sensitive (not all cancers cause tumour marker elevation). Some are used for screening, the prototypical example being PSA for prostate cancer, but because of the low specificity and sensitivity, this is controversial.
One of the main uses tumour markers is to monitor an already diagnosed cancer, often after treatment Following successfull cancer treatment, one expects the tumour marker level to drop or even normalise. If this does not occur, one can often assume that treatment was unsuccessfull. Following treatment, one can monitor the tumour marker regularly. A sudden increase in tumor marker is a sign of cancer recurrence.
However, as already mentioned, tumour markers are not sensitive, meaning that some cancer do not produce tumour markers. In these cases, tumour markers cannot be used to evaluate treatment response or monitor for recurrence.
Another main use of tumour markers is to evaluate the prognosis of a newly diagnosed cancer. If a cancer is diagnosed (or highly suspected), a significantly elevated tumour marker confers a worse prognosis than a non-elevated or only slightly elevated tumour marker, and may be a sign of locally advanced or metastatic disease.
Table of most important tumour markers
| Marker | Associated cancers |
|---|---|
| Human chorionic gonadotropin (hCG) | Trophoblastic tumours, nonseminomatous testicular tumours |
| α-foetoprotein (AFP) | Liver cell cancer, nonseminomatous testicular tumours |
| Carcinoembryonic antigen (CEA) | Colorectal cancer, pancreatic cancer, lung cancer, stomach cancer, |
| Prostate specific antigen (PSA) | Prostate cancer |
| CA-125 | Ovarian cancer |
| CA-19-9 | Colon cancer, pancreatic cancer |
| CA 15-3 | Breast cancer |
| Calcitonin | Medullary carcinoma of thyroid |
| Catecholamine and catecholamine metabolites | Pheochromocytoma |
| Ectopic hormones | Small-cell lung carcinoma, hepatocellular and pancreatic carcinomas |
| Prostatic acid phosphatase | Prostate cancer |
| Neuron-specific enolase | Small-cell lung cancer, neuroblastoma |
| Immunoglobulins | Multiple myeloma |
Those which are bolded are the most important.
Prostate specific antigen
Prostate-specific antigen (PSA) is an enzyme that is produced only by the prostatic glandular epithelium, which is why its level correlates to the number of prostatic glands in the body. Its level is elevated in prostate cancer but can also be increased in prostatitis or benign prostatic hyperplasia, so it’s not specific for cancer. PSA is considered elevated above 4 ng/mL. It should not be measured after digital rectal examination, as this artificially elevates the PSA.
In addition to measuring the total level of PSA, one can also measure other parametres such as free PSA, PSA density, PSA velocity, complexed PSA, and percentage of [-2]proPSA (a precursor of PSA). PSA in plasma is mostly bound to a carrier protein, while a small fraction is free. While decreased free PSA is known to be more specific for prostate cancer than total PSA, the clinical utility of the other parametres is not yet established and so they're not much used.
PSA is sometimes used for screening for prostate cancer, but this is controversial. Screening decreases mortality from prostate cancer but also causes overtreatment, as many of those who will receive cancer therapy (with all the complications and side effects it causes) due to detection of prostate cancer on screening would never have developed a clinically significant cancer. Elevated PSA might not necessarily correlate to a clinically active cancer, so its usefulness should be determined on a case-by-case basis. PSA does have great value in measuring the effectiveness of therapy though.
Alpha-foetoprotein
Alpha-foetoprotein (AFP) is a major plasma protein during foetal development, thought to be the foetal analogue of adult albumin. It is a tumour marker of several cancers, including hepatocellular carcinoma and non-seminoma testicular cancer.
Carcinoembryonal antigen
Carcinoembryonal antigen (CEA) is a tumour marker which is primarily associated with gastrointestinal cancers, including colorectal cancer, but can also be elevated in others like lung cancer and breast cancer. For unknown reasons, smokers have elevated CEA levels. CEA can also be elevated in benign gastrointestinal disorders like inflammatory bowel disease. Approximately 20% of colorectal cancers do not give elevated CEA.