Tumor markers are biological substances or metabolic products synthesized and released by cancer cells themselves or produced by the host in response to the presence of tumor. They will present in peripheral blood, serum, lymph nodes, bone marrow, stool, urine or other body fluids like ascites. A tumor also can be described as a comparatively autonomous growth of tissue. Most of the tumor markers are proteins and have short half-lives.
If something is to be considered a tumor marker, it should either not be present in healthy tissues or present at a very minimum level in healthy people and may present altogether patients with a selected malignancy. And also the amount of tumor marker in plasma should be proportional to the scale and activity of the tumor. Another important feature of a tumor marker is taken into account as its specificity to the tissue which it’s produced from. But a perfect tumor marker has not yet been identified. Tumor markers may be simply classified as follows in line with their functional and biochemical properties.
- Tumor antigens
- Tumor associated proteins
Alpha-fetoprotein (AFP), Carcinoembryonic antigen (CEA) are examples of oncofetal tumor antigens while ß HCG ( Human Chorionic Gonadotrophin), calcitonin, catecholamines, gastrin and insulin are considered as hormonal tumor markers. Enzyme tumor markers are prostatic acid phosphatase ( PAP ), Lactate dehydrogenase (LDH )and Neuron Specific Enolases (NSE). CA 125, CA 19-9, CA 15-3, Prostate-Specific Antigen ( PSA )are other tumour-associated proteins.
The uses of tumor markers are classified into 5 main areas as follows.
- Monitoring treatments
- Detection of recurrence
Apart from these main functions, early detection of cancer, staging of cancer, assessing the response to treatment and follow of a cancer patient are other uses of tumor markers. All the categories of the above-mentioned tumor markers are explained below with their specific uses.
1. CA 125
The normal blood level of CA 125 is a smaller amount than 35 U/ml. This is often usually called the tumor marker of ovarian cancer.It’s a cell surface glycoprotein normally expressed in the coelomic epithelium during fetal development. CA 125 get positive in gynaecological cancers like epithelial ovarian, endometrial, oviduct and Sertoli cell carcinomas. And also it detects non-gynaecological tumors like breast, colon, lung and pancreas carcinomas. This marker is especially wont to follow up women during or after treatment for ovarian cancer.
2. AFP – Alpha Fetoprotein
This is also a glycoprotein mainly synthesized by liver and fetal yolk sac. Normally this goes high in hepato cellular carcinomas ( HCC) and sex cell tumors. A traditional healthy person has but 15 ng /L of this marker. Levels above 1000 ng /L are mostly considered with cancer except in benign conditions as follows. Hepatitis ,pregnancy, biliary cirrhosis or habit. Useful in initial diagnosis, follow-up response to treatment, determine prognosis and detect recurrence early.
PAP (Prostatic acid phosphatase) was used earlier to detect adenocarcinoma but PSA is now used mainly thanks to its high sensitivity. It’s present in very low amounts in healthy which is a smaller amount than 4 ng /ml. In between 4 – 10, it’s called a gray zone which has 1 in 4 chance of getting an adenocarcinoma. Over10 means cancer is probably going. Diagnosis and follow from prostatic adenocarcinoma, monitoring recurrence and response to treatments are the main uses of this tumor marker. And this is often also a rare marker that is employed for screening and early detection of cancer.
A glycoprotein antigen used to watch the response to treatment, detect recurrence early and monitor whether there is a tumor regression or progression in metastatic diseases using serial values. Aside from colorectal, breast, gastric and pancreatic cancers, CEA levels also get elevated in 19% of smokers and three in the healthy population who are with benign conditions like peptic ulcers, inflammatory bowel disease or cirrhosis.
5. ß hCG – Tumor markers
A polypeptide is produced by the trophoblast cells of the normal placenta and elevated during pregnancy This often consists of alpha and beta subunits where beta subunit is particular for HCG . hCG level in the blood rises up in sex cell tumors and in gestational trophoblastic disease where the extent exceeds 100000 IU/L. Another important point is that ß HCG cannot cross the blood-brain barrier (BBB). So CSF: Serum ratio but 1: 60 is suspicious of cerebral metastasis.
Uses:- Initial diagnosis of testicular or ovarian cancer. Prognosis Detect recurrence earlier. Follow-up response to treatments.
6. Calcitonin – Tumor markers
A hormone produced by the parafollicular C cells of the thyroid. the most important function of calcitonin is to control the blood calcium level. This hormone elevates in malignant conditions like MTC, lung cancers and also in benign conditions like thyroid nodules. Use in early diagnosis of MTC ( Medullary Thyroid Carcinoma) and follow from the patient during or after treatment.
7. ER and PR – Tumor markers
Immuno histochemistry (IHC ) is employed to check for ER and PR in carcinoma tissues. ER may be a protein found within the nucleus of the breast and uterine. They act as predictors of prognosis and PR also has the identical prognostic value as ER and is measured by simple methods.
Detection methods of tumor markers
- Immunological methods ( ELISA ,IFA)
- Mass spectrometry
Let’s see on few of the drawbacks related to tumor markers…
- They’re present in very low concentrations in tissues with small early stage cancer.
- Lack of reliability
- Cancer cells moreover as most of the conventional cells can produce tumor markers.
- Sometimes although high level of tumor markers present, they will not be specific enough to verify