Tumor Markers- Lecture-5

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 the cell membranes or in the cytoplasm of the cell.
• Radioimmunoassay, Enzyme immunoassay 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 amounts in fetal life, but after birth, these antigens disappear and are present in a 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, the best marker of colorectal carcinoma.

b) Alpha-fetoprotein (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 the 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 the 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 the thyroid and pancreatic carcinoma
• Calcitonin- Medullary carcinoma of the 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. The 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 the thyroid and pancreatic carcinoma
10.	Calcitonin	Medullary carcinoma of the 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