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Tumor markers

Tumor markers are hormones, enzymes, peptides or proteins abnormally synthesized and released by the cancer cells, or are produced by the host cells in response to cancerous growth.

Tumor markers may be present in the body fluids, blood, cell membranes or in the cytoplasm of the cell.

Clinical significance of tumor markers

Tumor markers are used as diagnostic and prognostic agents. They are used -

  • For screening of  cancer in asymptomatic individuals
  • As an adjunct in clinical staging of the cancerous condition
  • For monitoring during cancer treatment
  • For early detection of recurrence of the cancerous process.

Techniques of estimation

Tumor markers can be detected by -

  • Immunohistochemistry if they are present on cell membrane or in  cytoplasm of cell.
  • Radio immuno assay, Enzyme immuno assay or Immunochemical reactions if they are found in blood circulation.

Classification of tumor markers

The clinically important tumor markers are as follows-

 1) Tumor associated antigens- These are also called oncofetal proteins/antigens. The properties of cancer cells are changed and they start producing abnormal products from the mutated/ altered oncogenes.

The tumor associated antigens are produced in large amount in fetal life, but after birth these antigens disappear and are present in very minute amount in adults. In malignant cells, the synthesis of oncofetal antigens is reactivated and their concentration in blood and cancer cells in increased.

Examples of oncofetal antigens-

a) Carcinoembryonic antigen (CEA)- Gastrointestinal cancer, ovarian, breast, cervical and lung cancers , best marker of colorectal carcinoma.

b) Alpha feto protein (AFP)- Germ cell tumor and hepatocellular carcinoma

c) Tissue polypeptide antigen- Colonic cancer, breast and prostatic cancer.

 Other less important antigens are-

  • Pancreatic oncofetal antigen
  • Colon specific antigen
  • Beta oncofetal antigen

 2) Carbohydrate antigens

These antigens are more specific in determining the site of tumor. They are organ and tissue specific.

Examples of  important carbohydrate antigens are-

a) CA-125-Mainly ovarian cancer, but may also be elevated in endometrial cancer, fallopian tube cancer, lung cancer, breast cancer and gastrointestinal cancer.

b) CA-15-3- Breast cancer

c) CA-19-9-Mainly pancreatic cancer, but also colorectal cancer and other types of gastrointestinal cancers.

d) CA- 27-29- Breast cancer.

3) Pregnancy associated antigens

a) Human chorionic gonadotropin-β-subunits- (β-HCG)- It is a placental hormone, synthesized by the syncytiotrophoblastic cells of placental villi. In the non pregnant state it is present only in very minute concentration in the serum, but it is markedly elevated in pregnancy. The peak level is attained at 12 weeks of pregnancy, then it declines slowly to reach 1/5 th of peak at the end of 20 weeks and continues at a very low level for a few days even after parturition.

Measurement of HCG in serum and urine is undertaken to diagnose pregnancy.

Chemically it has two subunits-α and β-subunits.

The beta subunit is typically measured, because of its increased specificity and because some tumor cells secrete only Beta subunit.

Its high level is an ideal marker of gestational trophoblastic and germ cell tumors of testes and ovaries.

Its high level is also observed in Seminoma, embryonal carcinoma, teratocarcinoma and choriocarcinoma.

b) Placental like Alkaline phosphatase-(Regan isoenzyme- PLAP)- The Regan isoenzyme is a placental-type alkaline phosphatase that is expressed in a number of human tumors, particularly in gonadal and urologic cancers.

c) Other antigens

  • Human placental lactogen (HPL)
  • Sex hormone binding protein (SHBG)
  • Steroid binding β globulin (SBBG)
  • α2 Pregnancy associated globulin (PAG)

4) Mammary associated antigens

  • MCA (Mucin like carcinoma associated antigen)- Breast cancer
  • MAM- Breast cancer
  • MSA (Mammary serum antigen)- Breast cancer
  • MAP(Mitogen activated protein kinase)- Breast cancer

5) Hormones used as tumor markers

  • ACTH- Lung cancer, Medullary carcinoma of thyroid and pancreatic carcinoma
  • Calcitonin- Medullary carcinoma of thyroid
  • Catecholamines- Pheochromocytoma
  • Gastrin- Gastrinoma
  • Insulin- Insulinoma
  • Glucagon- Glucagonoma
  • Serotonin Carcinoid syndrome

6) Enzymes and Isoenzymes used as tumor markers

a)  Lactate dehydrogenase (LDH)

  • Total LDH- Lymphoma, leukemia, germ cell tumor, breast and lung cancer
  • LDH1- Germ cell tumors, ovarian carcinoma, Osteosarcoma
  • LDH 2,3,4- Leukemias
  • LDH-5- Hepatoma , breast cancer, colorectal cancer and other benign liver diseases

 b) Alkaline phosphatase (ALP)

  • Liver isoenzyme- Metastatic liver cancer
  • Bone isoenzyme- Metastatic bone disease, benign bone disease
  • Regan isoenzyme- Lung cancer, ovarian cancer, breast cancer, colonic cancer and uterine cancer
  • Nagao isoenzyme- Metastatic carcinoma of pleural surfaces, adenocarcinoma of pancreas and bile duct.

 c) Acid phosphatase

  • Prostatic acid phosphatase- Prostate cancer

 d) Creatine Kinase

  • CPK- BB- Adenocarcinoma, prostatic carcinoma

 e) α1- Antitrypsin- Germ cell tumor of testes and ovaries.

 f) Neuron specific Enolase- Neuroblastoma and Lung cancer

7) Miscellaneous tumor markers

  • Prostate specific antigen- Carcinoma prostate
  • Mono clonal immunoglobulins
  • Polyamines

Summary Table

S.no Tumor marker Significance
1. Carcinoembryonic antigen (CEA) Gastrointestinal cancer, ovarian, breast, cervical and lung cancers. Best marker of colorectal carcinoma. 
2. Alpha feto protein (AFP)  Germ cell tumor and hepatocellular carcinoma
3. Tissue polypeptide antigen.   Colonic cancer, breast and prostatic cancer
4. CA-125 Mainly ovarian cancer, but may also be elevated in endometrial cancer, fallopian tube cancer, lung cancer, breast cancer and gastrointestinal cancer
5.  CA-15-3  Breast cancer
6. CA-19-9 Mainly pancreatic cancer, but also colorectal cancer and other types of gastrointestinal cancers. 
7. β-HCG Gestational trophoblastic and germ cell tumors of testes and ovaries
8.  MAP(Mitogen activated protein kinase) Breast cancer 
9. ACTH Lung cancer, Medullary carcinoma of thyroid and pancreatic carcinoma 
10. Calcitonin  Medullary carcinoma of thyroid 
11. Catecholamines Pheochromocytoma 
12. Gastrin- Gastrinoma 
13. Insulin Insulinoma 
14. Glucagon- Glucagonoma 
15. Serotonin Carcinoid syndrome 
16. Total LDH Lymphoma, leukemia, germ cell tumor, breast and lung cancer 
17. Alkaline phosphatase (ALP)  Metastatic liver cancer, bone disease, lung and gonadal cancers 
18. Acid phosphatase Prostate cancer
19. Prostate specific antigen Prostate cancer

 

 

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