Al-Dubai, Medical Biochemistry

Chapter 12
Biochemistry of cancer

Cancer is a group of diseases due to unregulated cell growth. The term

“cancer” is derived from Latin word “cancrum” or Greek “karkinoma”, which
means “crab”.It is called cancer because of swollen veins around the cancer
which resemble a crab’s limbs. Cancers represent the second most common
cause of death after cardiovascular diseases in many countries, about 8
million of people around the world die from cancer each year.The incidence of
many cancers increases with age (due to prolonged exposure to carcinogens and
accumulation of mutation).

Table 12.1 Prevalence of cancers in the world in 2012

Rank Type of cancer Percentage % No of cases in million
1 Lung 13 1.8
2 Breast 11.9 1.6
3 Colorectum 9.7 1.3
4 Prostate 7.9 1.1
5 Stomach 6.8 0.95
6 Liver 5.6 0.78
7 Others ---------- ----------
Note:
Lung cancer was the most common cancer worldwide in men but in women
Breast cancer was the most common cancer.
The tumors can be classified into:
1-Benign tumor is unregulated proliferation of cells which does not invade or
spread to other organs of the body. Normally benign tumors are not life-
threatening (e.g. moles, warts, cysts, polyps).
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2-Malignant tumors or cancers are uncontrolled proliferation and spread of cells

to various organs of the body where they can continue to grow and form another
tumor at that site, this is known as metastasis or secondary cancer. Malignant tumors
are life-threatening (e.g. lung cancer).

Cancers also can be classified according to their tissue of origin:

A carcinoma is derived from epithelial tissue
A sarcoma is derived from connective tissues
Leukemia refers to tumors of the bone marrow
Lymphoma refers to a tumor which arises from lymphoid tissue
Characteristic of malignant tumor cells

A-General characteristics

1- Proliferate rapidly (loss of normal growth control)

2- Loss of contact inhibition in vitro (malignant cells grow in multilayers but normal
cells form monolayer).

3-Invade local tissues and spread, or metastasize, to other organs of the body

4-Stimulate local angiogenesis

5- Able to avoid apoptosis

6-Can grow without attachment to the surface but normal cell adhere to the surface

7-The tumor cells are more rounder in shape than normal cells and have more
chromatin

8-Need little amount of growth factor for their growth but can produce large
amount of growth factors.

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B-Biochemical and genetic changes in malignant cells

1- Increased replication and transcription ( Increase synthesis of DNA and RNA).

2-Increased aerobic and anaerobic glycolysis due to increase energy demands.
3- Synthesis of fetal proteins (e.g.carcinoembryonic antigen, alfa fetoprotein).
4-Changes in the structure of glycoproteins and glycolipids (due to addition of
abnormal sugar chains).
5- Hypercalcaemia , many cancer can produce parathyroid hormon -related
peptide or osteoclast-activating cytokines which activates osteoclast which
lead to dissolve bone matrix. (e,g multiple myloma).
6-Hyperurecemia due to increase catabolism of purine
7-Increase synthesis of growth factors and hormones and some enzymes
8-Precence of occult blood in stool (e.g colon cancer).
Hidden
9- Increases synthesis of clotting factors which may lead to increase risk for
thrombosis.
10-Release of biomarkers ( measurable substances which indicate to presence
of a disease).
11-Increase mutations and chromosomal abnormalities
12-Increase telomerase activity
Causes of cancer

Cancer is a disease caused by genetic mutations due to carcinogenic factors, causes of

cancer can be classified into:

A- Environmental factors or exogenous factors

Environmental factors or exogenous factors can be subdivided into:

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1-Chemical factors

Many of chemicals are known as mutagens (any agent that cause genetic
mutation) and carcinogens (any agent that cause cancer).About 80% of human
cancers are caused by environmental factors, especially chemical substances.
a-Cigarette
Cigarette contains many carcinogens,but the most important compound is
called benzo(α)pyrenes (polycyclic aromatic hydrocarbones) which may
cause point mutation in the p53 gene, a tumor suppressor gene.
b-Aflatoxins
Aflatoxins are strong carcinogens, which produce hepatomas, They are
synthesized by the fungi, Aspergillus flavus. Aflatoxins produce cancer by
mutation in p53 gene.
c-Nitrosamines which can form mutations by deamination of nucleotides

d-Drugs like alkalyting agents (e.g, cyclophosphamide used as chemeotherapy),

which add methyl group to guanine which lead to DNA crosslink.

f-Metals like cadmium

2- Physical factors

a-Ionized radiation

Ionized radiation like X-ray or γ-ray , produce free radicals which damage the DNA

b-Ultraviolet ray

Ultraviolet ray lead to thymine dimer which may lead to skin cancer

3-Biological factors

Biological carcinogenic factors include some types of viruses (both DNA and
RNA viruses), about 15% of human cancers may be caused by viruses, the
genetic material of viruses is incorporated into the genome of the host cell.
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Table 12.2 Some viruses which cause or associated with human cancers
Type of virus Type of genome Type of cancer
Epstein-Barr virus DNA Burkitt lymphoma, nasopharyngeal
cancer, B cell lymphoma
Hepatitis B DNA Hepatocellular carcinoma

Hepatitis C RNA Hepatocellular carcinoma

Human herpes virus type 8 DNA Kaposi sarcoma
Human papilloma DNA Cervix Cancer
viruses type 16 and 18
Human T-cell leukemia virus RNA Adult T-cell leukemia
type 1
B-Endogenous factors

a-Metabolic activity that produces free radicals

b-Spontaneous mutations
c-Genetic diseases (e.g. Xeroderma pigmentosum)
Molecular mechanism of cancer (carcinogenesis)
Cancer is a genetic disease caused by a mutation which lead to abnormal
increase or decrease in the expression of specific genes, two types of
regulatory genes called proto-oncogenes and tumor supresser genes
(antioncogenes) are involved in the development of cancer and a third type
of genes which control apoptosis (the programmed cell death) are believed to
be involved in carcinogenesis.
1-Proto-oncogenes
Proto-oncogenes are genes which produce proteins that stimulate cell growth
and cell division, these proteins include growth factors, growth factor receptors,
hormone receptors, signal transducers (e,g enzymes like protein kinase A), and
transcription factors. Mutation in proto-oncogenes (autosomal dominant
mutations) may convert proto-oncogenes into oncogenes (oncogenes produce

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oncoproteins which lead to the transformation of a normal cell into a tumor

cell) which lead to increase production of proteins or increase production of
altered protein that does not respond to normal signals. Proto-oncogenes are
converted to oncogenes by:
a- A point mutation or a deletion in the coding sequence which lead to the
formation of a protein with an abnormally high activity.
Note:
a-Mutation can be classified according to effect on function into many types,
for example:
1-Gain-of-function mutations (activating mutations), are mutation which
increase the activity of protein. It is dominant mutation.
2- Loss-of-function mutations (inactivating mutations), are mutation which
decrease the activity of protein. It is recessive mutation.
b-Mutation in a single gene is not sufficient to produce cancer.

Figure 12.1 Molecular mechanism of cancer due to mutation in proto-oncogenes

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For example:
1-HER2 (human epidermal growth factor receptor 2)
Point mutation in proto-oncogene HER2 in long arm of chromosome 17 lead
to changes a valine to glutamine in this receptor which lead to activation of
this receptor in absence of growth factor, it is observed in some breast
cancers.
2-EGF receptor (epidermal growth factor receptor)
Deletion of small part of the EGF receptor gene lead to formation of EGF
receptor which lacks the extracellular ligand-binding domain but lead to
activation of this receptor in absence of growth factor, it is observed in
glioblastoma.

Figure 12.2 Molecular mechanism of cancer due to mutation in proto-oncogenes

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b- Gene amplification ( multiple copies of gene), which caused by abnormal DNA

replication, that leads to multiple copies of a proto-oncogene, which result in an
overproduction of the normal protein (not oncoprotein) which lead to growth
stimulation (e.g., HER2 which observed in breast cancer).

c- Chromosomal translocation is a type of genetic rearrangement which lead

to make a proto-oncogene under the control of a different and strong promoter
or produce a fusion protein that is more active, for example:
a-ABL (Abelson murine leukemia viral) proto-oncogene
The ABL1 proto-oncogene produce cytoplasmic and nuclear protein called
tyrosine kinase which has a role in cell differentiation, cell division, and cell
adhesion found in long arm of chromosome 9.Translocation between
chromosome 9 and chromsome 22 lead to form Philadelphia chromosome
(chromosome 22 after translocation)which produces the BCR-ABL fusion
oncoprotein ( unregulated tyrosine kinase) which causes chronic myeloid
leukemia (CML).

Figure 12.3 Molecular mechanism of cancer due to mutation in proto-oncogenes

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Note:

BCR (breakpoint cluster region protein) is a gene produce serine/threonine kinase

2-Tumor supresser genes

Tumor supresser genes are genes which produce proteins that involved in the
control of cell proliferation, especially those that regulate the cell cycle
checkpoints (The cell cycle checkpoints are control mechanisms in eukaryotic
cell division), mutations in tumor suppressor genes are autosomal recessive
mutations which lead to loss the function of proteins (Loss-of-function
mutations). There are five types of proteins:
a- Proteins that regulate a specific phase of the cell cycle (e.g., RB protein in
G1 phase).
b- Proteins that monitor checkpoints to arrest the cell cycle (e.g., p53)
c- Proteins that are components of growth-inhibitory signaling pathways (e.g.,
APC protein)
d- Proteins that promote apoptosis (e.g., FAS, BAX)
f- Proteins that participate in DNA damage repair (e.g., Nucleotide excision
repair proteins implicated in xeroderma pigmentosum).

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Table 12.3 Mutations in tumor suppresser gene

Type of Gene Normal Function Characteristic of Mutated

Protein

P 53 It is found in chromosome 17, and Mutated P53 Observed

P= protein Monitors checkpoints of cell cycle in >50% of all human tumors

It is activated by damage to DNA.

I t is called guardian of genome,

because it prevents genome

mutations

RB It is found in chromosome 13, and Observed in retinoblastoma

(Retinoblastoma) Regulates G1 phase of cell cycle by

Binding to transcription factor

APC It is found in chromosome 5, and Observed in familial

(Adenomatous Regulates cell proliferation adenomatous polyposis, which

polyposis coli)
may convert into colon cancer

DCC It is found in chromosome 18, and Observed in colon cancer

(Deleted in Plays a role in cell proliferation,

migration, and apoptosis
Colorectal

Carcinoma)

BRCA 1/BRCA2 It is found in chromosome 17, and Observed in breast cancer;

inheritance of a mutated BRCA 1
(Breast Cancer) Plays a role in DNA repair and gene increases the chance of
developing breast cancer by the
Apoptosis
age of 50 by30-fold

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Cell Cycle

Cell cycle is sequence of events inside the cell which lead to cell growth and
cell division to form two daughter cells. The cell cycle consists of three stages
( growing, dividing, or resting). Each stage consists of some phases. The events
of the cell cycle are controlled and monitored to ensure that no errors are passed
to the progeny.
The cell cycle stages
1-Growing stage or called interphase stage
Interphase stage is subdivided into:
a-G1 (Gap 1 or Growth 1) phase
In G1 phase, exogenous growth factors stimulate RNA and protein synthesis
which is important for DNA replication, in the next phase.
b- S (synthesis) phase
In S phase, DNA is replicated, and RNA and proteins are synthesized.
c- G2 (Gap 2) phase
In G2 phase, RNA and protein synthesis continue, and the integrity of the
DNA is checked (proofreading) as the cell prepares to division.
2-Dividing stage or called M (mitotic) stage
In mitotic stage, nuclear division and cytoplasmic division occurs to produce
two identical daughter cells. This stage subdivided into:
a-Prophase (Chromatin condenses into chromosomes and nucleolus
disappears)
b-Metaphase (Chromosomes are line up in metaphase plate)
c- Anaphase (Chromosomes break at centeromers, and sister chromatids move
to the opposite ends of the cell)
d- Telophase (Formation of nuclear membrane,and nucleoli appear,and
chromsomes unwind into chromatin).

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f-Cytokinesis ( The cytoplasm of the cell is divided to form two daughter cells
by a contractile ring of actin and myosin filaments).
3-G0 phase (it is called resting or post-mitotic phase)
Most cells like bone marrow cells or intestinal cells, or skin cells not enter this
phase but enter G1 and undergo continuous rapid cell turnover , other cells
like nerve cells, cardiac cells or liver enter this phase( liver or cardiac cells
enter G1 phase if necessary). In this phase, the cell has left the cycle and has
stopped dividing.

Figure 12.4 Cell Cycle

Regulation of cell cycle

Cell cycle is regulated during embryogenesis or after birth by regulatory

proteins called cyclins and cyclin dependent kinases (CDK) . Cyclins form
complexes with cyclin dependent kinases to stimulate the kinase activity of the

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CDK by autophosphorylation , then, the active cyclin-CDK complex catalyzes

the phosphorylation of other proteins on serine and threonine amino acid
residues (at hydroxyl group), these activated proteins activated cell cycle. There
many types of cyclins and cyclin dependent kinases.

Note:

1-Increase phosphorylation of cyclin-CDK complex inhibits this complex

2-Decrease phosphorylation of cyclin-CDK complex activates this complex

Table 12.4 Function of cyclins and cyclin dependent kinase

Type of Cyclin Type of Cyclin Function

dependent kinase (CDK)

Cyclin A & E CDK2 Activate proteins which is important

for initiation of DNA synthesis in
early S phase
Cyclin B CDK1 Activate proteins which is

important for initiation of mitosis

Cyclin D CDK4 & CDK6 Helps the passage of cells

through the restriction point

in the end of G1 phase

Note:

1-The restriction point (R-point) is a transition point in the end of G1 of the cell
cycle at which the cell becomes committed to enter the S phase of the cell
cycle and to complete the cycle due to extracellular stimulants (mitogen).
Before the restriction point, a cell requires extracellular stimulants like growth

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factors to enter the cycle, but after the restriction point has been passed , the
growth factor signals are not needed.

2-Growth factors Stimulate synthesis of cyclins and cyclin dependent

kinases When cyclin dependent kinase binds with cyclin it become
active cyclin and cyclin dependent kinase complex inhibits tumor
suppresser gene in G1 phase called RB (retinoblastoma) by phosphorylation
which lead to release the transcription factor called E2F from RB binding site
which stimulate the synthesis of Cyclin A & E which is important for DNA
synthesis in early S phase.

3-Human papillomavirus types 16 and 18 can cause cervical cancer because, in

infected cervical cells, viral protein E6 binds to p53 and viral protein E7 binds
to RB which lead to inactivated these tumor suppressor genes which lead to
unregulated cell cycle which lead to cervical cancer.
4-Mitogen is a substance that stimulates mitosis.
5- Tumor suppresser gene RB (retinoblastoma) is inactivated by
phosphorylation or by binding with transcription factor E2F, phosphorylation
of RB lead to release transcription factor E2F from RB binding site which
stimulate the synthesis of Cyclin A & E which is important for DNA synthesis
in early S phase.

Checkpoints of cell cycle

Checkpoints located at specific points in the cell cycle to monitor the integrity
of DNA and separation of chromosomes by arresting cell cycle at specific point
in order to repair the damage. There are three checkpoints:
A-G1 checkpoint

G1 checkpoint confirms the integrity of DNA during the end of G1 phase,

before continue to S phase. When DNA is damaged by physical or chemical

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agents, replication of DNA before repair and segregation of damaged

chromosomes may lead to transmitting the damage to the daughter cells, so for
integrity of DNA, any damage to the DNA will induce molecular mechanism
which arrest the cell cycle at the checkpoint to give enough time for repair

Molecular mechanism of cell cycle checkpoint

The DNA damage activates protein kinase called ATM (Ataxia telangiectasia
mutated),which activate checkpoint kinase that phosphorylates and stabilizes
the p53 protein, activated p53 increases the transcription of protein called
p21, (a CDK inhibitory protein), binding of p21 with CDK lead to inhibit
cyclin-CDK complexes, which lead to arrest the cell cycle in G1, G2 and S
phase for repair, but if the damage is not repaired, then the cell undergoes a
process called apoptosis (a programmed cell death) or permanent loss the
ability of proliferation.

Note:
In the absence of DNA damage, p53 is inhibited by Mouse double minute2
(mdm2) is a protein which inhibits tumor suppresser gene p53 by two
methods:
1-Dgredation the p53 through binding p53 with ubiquitine which increase
degradation of p53 by proteosome ,

2- Inhibition the transcription of p53

Mdm2 is first isolated from small, extrachromosomal bodies present in a

mouse cell line , so called mouse double minute.
B-G2 checkpoint

G2 checkpoint confirms the integrity and completeness of DNA replication

during G2 phase,before continue to M phase.

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C- Metaphase checkpoint

Metaphase checkpoint monitors the attachment of chromosomes to the mitotic

spindle fibers before continue into anaphase and monitors segregation of

chromosomes during mitosis.

Figure 12.5 Molecular mechanism of cell cycle checkpoint

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Apoptosis

Apoptosis is a programmed cell death (from the Greek word means "The falling
off of the leaves"). About 50 billion cells die each day due to apoptosis in
adult but about 20 billion in children. Apoptosis is a genetically regulated form
of cell death which has a role in embryogenesis, ageing, and many diseases.

Function of apoptosis

1-Apoptosis is used to remove unneeded cells during embryo development

(e.g., formation of fingers and toes).
2-Elimination of damaged cells due to virus, radiation, or toxins.
3-To keep the number of the cells in normal healthy adult at relatively constant
level as a result of a balance between cell division and cell death.

Mechanism of apoptosis

Apoptosis is performed by enzymes called caspases (intracellular proteases)

which are synthesized as inactive enzymes called procaspases which activated
by cleavage by other caspases at aspartic acid residues. There are two major
mechanism for the induction of apoptosis. Both pathways lead to
mitochondrial damage which trigger a caspase cascade.
1- Extrinsic pathway (also called the death receptor pathway)
a-This pathway is triggered by the binding and activation of an external death
ligand (a molecule, as protein , hormone, or drug, that binds to a receptor) like
tumor necrosis factor-α (TNF-α) , or Fas ligand (fasL)) to its receptor on the
plasma membrane which called tumor necrosis factor-α receptors and Fas
receptor which activated adaptor protein(a connecting molecule) which called
Fas associated death domain protein (FADD) and tumor necrosis factor
receptors type-1 associated death domain protein (TRADD) which convert
procaspase 8 to active caspase 8 , which activates other caspases called caspase

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3, 6, and 7 which kill cell by digesting many proteins of the cell and DNA of
the cell.
b-Also Caspase-8 converts the cytosolic pro-apoptotic activator protein called
BID to active form called truncated BID (tBID) which acts on mitochondrial
pro-apoptotic effector proteins called BAK and BAX to initiate cytochrome-c
release which binds to adaptor protein called apoptotic peptidase activating
factor-1 (APAF-1) to form apoptosome, which converts procaspase-9 into
active caspase-9 which activates other caspases called caspase 3, 6, and 7 which
kill cell by digesting many proteins of the cell and DNA of the cell.
Regulation of extrinsic pathway
This pathway regulate by:
1- FLIP (FLICE-like inhibitory protein) which inhibits the conversion of
procaspase-8 to active caspase-8.
2-Inhibitors of apoptosis (IAPs) which inhibit the conversion of procaspase-3
to active caspase-3.These effects can be overcome by the protein SMAC,
(second mitochondrial-derived activator of caspase), which is released from
mitochondria.
2-Intrinsic pathway (the mitochondrial pathway)
Intrinsic pathway is triggered by cellular stress, like DNA damage (which
increases p53), or growth factor withdrawal, cell cycle defects and exposure to
cytotoxic drugs which lead to increase permeability of mitochondria which lead
to release of cytochrome-c from mitochondria (Cytochrome-c release is
facilitated by pro-apoptotic proteins BAX and BAK, which find in the outer
mitochondrial membrane) which binds to adaptor protein called apoptotic
peptidase activating factor-1 (APAF-1) to form apoptosome, which converts
procaspase-9 into active caspase-9 which activates other caspases called
caspase 3, 6, and 7 which kill cell by digesting many proteins of the cell and
DNA of the cell.

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Regulation of intrinsic pathway

This pathway regulate by:
1-The relative amounts of BCL-2 protein family like anti-apoptotic proteins
which inhibit the release of cytochrome c and pro-apoptotic proteins called
BAX, and BAK proteins.
Note:
1-The BCL-2 family can be classified into three groups:

a-Anti-apoptotic proteins like, BCL-X, BCL-W, BCL-B

b-Pro-apoptotic effectors, like, BAX, BAK

c-Pro-apoptotic activators, like BID

2- BAX, and BAK found in the mitochondrial membrane, and when

stimulated by tBID, promote the formation of pores in the mitochondrial
membrane, initiating the apoptotic program by releasing cytochrome c.

3-Effector (‫ )المستجيب‬is a molecule that can response to stimulus.

4-Activator is a molecule that activate another molecule

5-Necrosis is the death of the cells in an organ or tissue due to disease, injury,
or failure of the blood supply.

Apoptosis and diseases

1-In case of human immune deficiency virus (HIV) , the virus increase the rate
of apoptosis of T- helper cells (CD4 lymphocytes) which lead to depletion of
T- helper cells which lead to acquired immune deficiency syndrome (AIDS).
2- In some types of cancer, there is inhibition of apoptosis due to increase
synthesis of apoptosis inhibitors.
3-In Alzheimer's disease (neurodegenerative disease), amyloid protein increases
and may induce apoptosis of brain cells.

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Figure 12.5 Mechanism of apoptosis

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Table 12.5 Differences between apoptosis and necrosis

Characteristics Apoptosis Necrosis

Stimuli Physiological or pathological Pathological (injury)

Occurrence Single cells Groups of cells

Cell shape Shrinkage and formation of Swelling and later

apoptotic bodies disintegration

Adhesion between cells Lost (early) Lost (late)

Phagocytosis by other cells Present Absent

Membranes Blebbing Blebbing proir to lysis

Gene activation Present Absent

Requirement for protein Present Absent

synthesis

Lysosomal enzyme release Absent Present

Activation of caspases Present Absent

Level of ATP required High Low

Laboratory test used for cancer diagnosis

1-Biopsy ( is the gold standard test for cancer)
Biopsy is a small specimen of tissue which removed from a part of the body for
examination under a microscope by a pathologist.
2-Fine needle aspiration (FNA) for cytology
In fine needle aspiration a thin needle is inserted into an area of abnormal-
appearing tissue or body fluid.
4-Bone marrow aspiration 5-Measurment of tumor markers

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Tumor markers

Tumor markers are substances like serum proteins, hormones, metabolites,

receptors , oncofetal antigens (are proteins produce only during fetal development
and in adults who have cancer), and enzymes which present in body fluids or
tissues, which provide information about the presence, or progression or remission of
tumors. Tumor markers may be produce from the tumor cells or produce from
normal cells as a result of metabolic effect of tumor cells.

Application of tumor markers

Tumor markers may be used for :
1-Screening for disease (Very few markers are sensitive or specific to be used
to screen for the presence of a tumor.
2-Diagnosis tumors, if a patient presents with clinical signs or symptoms, the
measurement of tumor markers in serum or urine may be used to confirm a
diagnosis.
3-Determine the prognosis because in some cases the concentration of a
specific marker is related to the size of the tumor or spread of the tumor.
4-Monitoring the response to treatment , if a tumor marker is present, the rate
of its decrease in concentration may be used to assess the response to treatment
(like surgery, chemotherapy or radiotherapy).
5-Identification the recurrence of a tumor.

Characteristics of a tumor markers which can be used in diagnosis

1- High specific (Increase only in one tumor type)
2-High sensitive ( Not-detectable in normal case or benign tumor)
3-Can be measured by simple and cheap test

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Classification of tumor markers

Table 12.6 Classification of tumor markers based on origin, biochemical properties,
and biological function.
Types Example
Oncofetal antigens Alfa fetoprotein (AFP)
Carcinoembryonic antigen (CEA)
Squamous cell carcinoma antigen (SCC)
Tissue polypeptide antigen (TPA)
Hormones Catecholamines, Calcitonin, β-hCG
ACTH, Prolactin
Carbohydrate antigens CA 125, CA 15-3
CA 19-9, CA 72-4
(CA mean Carbohydrate antigen or Cancer
antigen)
Prostate-specific antigen (PSA)
Metabolites Vanillylmandelic acid (VMA)
Hydroxy indole acetic acid (HIAA)
Metanephrine
Proteins Immunoglobulins, β-2-Microglobulin
C- peptide , Ferritin
Enzymes Lactate Dehydrogenase (LDH)
Alkaline phosphatse (ALP)
Neuron-specific enolase (NSE)
Prostatic acid phosphatase (PAP)
Receptors Estrogen receptor (ER)
Progesterone receptor (PR)
Oncogene products c-myc, c-erbB2
Myelocytomatosis cellular gene (c-Myc), produces transcription factor seen in
Burkitt lymphoma.
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Table 12.7 Applications of common tumor markers

Malignancy Tumor marker Uses for
Adrenal carcinoma Steroids, Catecholamines Diagnosis
Breast Cancer CA 15-3, CA 27-29 Monitoring , Recurrence

Estrogen receptor Monitoring (Response to therapy)

Progesterone receptor

Carcinoid tumor HIAA Diagnosis

Colorectal cancer CEA, CA 19-9 Prognosis, Monitoring
stomach, pancreas
Choriocarcinoma β-hCG Diagnosis, Prognosis, Monitoring
Hepatoma AFP Screening,Diagnosis, Prognosis
Monitoring
Melanoma Tyrosinase Diagnosis
Myeloma Immunoglobulins Diagnosis, Prognosis
Ovarian cancer CA 125 Diagnosis, Monitoring ,Recurrence
Prostate cancer PSA Screening, Diagnosis, Prognosis
Monitoring
Thyroid cancer Thyroglobulin Screening, Monitoring

Calcitonin Screening, Monitoring, Prognosis

Lung cancer Neuron-specific enolase Diagnosis

SCC, TPA
Bladder cancer Bladder Tumor Antigen Diagnosis
(BTA) (urine test)
Renal cancer Erythropoietin
Bladder Tumor Antigen
Ferritin (not good)
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Note:
1-Carcinoid tumor is a tumor occurring in the glands of digestive system or
lung which secreting hormones.
2- Choriocarcinoma a malignant tumor of the uterus that originates in the cells
of the chorion of a fetus, and may arise in the testis or ovary.
3-Prostate specific antigen (PSA) is an enzyme produced by epithelial
prostatic cells, in both benign and malignant cases, which break down the high
molecular weight protein of the seminal coagulum.
4-Most PSA in the blood is bound to serum proteins and small amount is found
as free PSA (not bound to proteins). In men with prostate cancer the ratio of
free PSA to total PSA is decreased. Studies have shown that, the risk of cancer
increases if the percentage of free PSA is less than 25% in patients with a total
PSA level between 4 ng/ml and 10 ng/ml, and the patient need biopsy.
5- Both total and free PSA increase immediately after ejaculation, and returning
slowly to baseline levels within 24 hours.
Table 12.8 Some benign conditions associated with rise in some tumor markers
Tumor markers Benign conditions
AFP Viral hepatitis, liver injury, pregnancy, IBD
CEA Smokers, IBD, hepatitis, cirrhosis,
pancreatitis, gastritis,
CA 125 Peritonitis, pelvic inflammatory disease,
pregnancy
CA 19-9 Pancreatitis, hepatitis
Prostatic acid phosphatase Prostatitis, benign prostatic hyperplasia
Prostate-specific antigen
β-hCG pregnancy
Inflammatory bowel disease (IBD) involves chronic inflammation of all or part of
digestive tract (e.g., ulcerative colitis)

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