TUMOR MARKERS

Dr. HESHAM ANWAR

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# Cancer is a serious disease

characterized by excessive, uncontrolled
growth of abnormal cells, which invade
and destroy other tissues
# Cancer develops in almost any organ or
tissue of the body, but certain types of
cancer are more lethal than others
# For reasons not well understood,
cancer rates vary by gender, race, and
geographic region
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# Cancer usually develops gradually over

many years, the result of a complex mix
of environmental, nutritional, behavioral,
and hereditary factors
# Cancer mechanism is not completely
understand, but certain lifestyle choices
can dramatically reduce the risk of
developing most types of cancer
# Not smoking, eating a healthy diet, and
exercising moderately for at least 30
minutes each day reduce cancer risk by
more than 60 percent
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Tumor formation
# A tumor is a mass of cells can grow on
top of each other, creating a mass of
abnormal cells
# Often a tumor develops its own network
of tiny blood vessels to supply itself with
nutrient-rich blood, a process called
angiogenesis
# There are two general types of tumors :
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1- Benign tumors which do not invade other

tissues and are limited to one site, with
possible surgical removal & recovery
# Some benign tumors are harmless and are
not surgically removed unless they are
uncomfortable
# For example, warts are benign tumors of
the outer layer of the skin
# Although they are usually not dangerous,
warts may cause discomfort
# Some benign tumors considered
precursors to malignant tumors
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2- Malignant Tumors are those ones who

can invade other parts of the body
# Malignant tumors extend into
neighboring tissue or travel to distant
sites, forming secondary growths known
as metastases
# To metastasize, tumor cells break
through a nearby blood vessel to enter
the circulatory system or through a
lymphatic vessel wall to enter the
lymphatic system
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TNM staging of a tumor

T = Tumor differentiation
(T1 = well differentiated T2 = poorly
differentiated, T3 = anaplastic i.e. without
form & T4 = Unknown shape)
N = Number of lymph nodes
(N0 = No lymph nodes, N1 = 1-5 LN,
N2 =6-10 LN & N3 more than 10 LN)
M = Presence of metastasis
M0 = no metastasis & M1 = +ve metastasis
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Definition of tumor marker

# A tumor marker is a substance present in
or produced by a tumor itself or produced
by the host in response to a tumor that can
be used to differentiate a tumor from
normal tissue or to determine the presence
of a tumor based on measurement in the
blood or other body secretions
# Such a substance can be found in cells,
tissues, or body fluids like Blood, Urine,
CSF, etc
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# It can be measured qualitatively or

quantitatively
# Tumor markers are the biochemical or
immunological parts, which can differentiate
stage and grade of the tumor
# An ideal tumor marker should be specific
for a given type of cancer and sensitive
enough to detect small tumors for early
diagnosis or during screening
# Tumor markers are most useful in
evaluating the progression of disease status
after the initial therapy and monitoring after
treatment (more than diagnosis)
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Classification of tumor markers

1- Enzymes & iso-enzymes were one of the first
groups identified
2- Hormones were used for the detection and
monitoring of cancer
3- Oncofetal antigens, such as AFP & CEA
4- More importantly, antigens e.g., PSA, CA125,
CA15-3 & CA19-9 (formed of glycoproteins or
mucins)
5- Finally, genetic markers & oncogene (gene
markers) could provide an information into the
progression from normal to benign, from benign
to primary disease, & from primary disease to
metastatic stages
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Clinical applications
of tumor markers
1- Screening in high risk population
2- Differential diagnosis in symptomatic patients
3- Clinical staging of cancer
4- Estimating tumor volume
5- Disease progression
6- Detecting the recurrence of cancer
7- Monitoring & evaluating the success of
treatment
8- Localization of tumor masses
9- Aid in define hormonal therapy like in breast
cancer patients
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CRITERIA FOR EVALUATING

TUMOR MARKERS
# The ideal tumor marker should possess
the following properties:
1- High specificity, i.e. the marker is not
detectable in benign diseases and
healthy subjects
2- High sensitivity, i.e. the marker is
detectable very early when only a few
cancer cells are present
3- Organ specificity e.g. PSA, PAP
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4- Correlation with the tumor stage or

tumor mass
5- Correlation with prognosis
6- Reliable prediction value
7- The criteria of 100% specificity & 100%
sensitivity
# Unfortunately that criteria have not yet
been fulfilled by any of the known tumor
markers
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Nonspecific elevations
of tumor markers
# Some non-pathological conditions may result
in increased serum levels of tumor markers as:
CONDITION
Pregnancy
Menstrual cycle
Smoking

MARKER(S)
AFP,HCG,CA125, TPS
CA125
CEA, TPS, TG

Alcohol
Iron therapy & Blood
transfusion

CEA, TPS
Ferritin

Bladder catheterization

PAP, PSA
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# Non-neoplastic pathological conditions

resulting in increased serum tumor markers
CONDITION
Jaundice

MARKER(S)
CEA,TPS,Ferritin,CA19-9

Chronic bronchopneumonia
Ascites

CEA, TPS
CA 125

Endometriosis
Pancreatitis

CA 125
CA 19-9, CA I25

Chronic kidney disease

Prostatic hypertrophy

CEA, TPS
PAP, PSA

Urinary retention
Rheumatic disease

PAP, PSA
CA 19-9

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Frequency of tumor marker

determinations
1- Before therapy
(Operation, chemotherapy, hormonal therapy or
radiotherapy)
2- After operation or after starting therapy
# 2 to 10 days after therapy
# In intervals of 3 months during the 1st & 2nd
year
# In intervals of 6 months in the 3rd ,4th & 5th
year after the first therapy
3- Before any change of therapy
4- Under suspicion of relapse or metastases 16

BREAST CANCER
# Good prognosis is closely linked to
early diagnosis
# The risk of breast carcinoma decreases
with an increase in the number of
children a woman has born
# Hormonal influences increase the risk
of breast cancer
# Radiation exposure and dietary
influences (fatty diet) increase the risk of
breast cancer
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METASTASIS
# Lymphogenic to regional lymph nodes
# Distant metastases: bone, liver, lung,
pleura, ovaries & brain
# CA15-3 & MCA (Mucin-Like carcinomaassociated antigen) are the markers of
choice
# CEA is also used with the other
markers

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COLORECTAL CANCER
# Recovery rates of 85-100% are
observed in stage I disease, but this
declines to 70% in stage II and to only
30-60% in stage III
# CA19-9 is the marker of choice
# CEA & TPS (Tissue polypeptidespecific antigen) are also used with the
other marker
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LIVER CANCER
# Risk factors include liver cirrhosis,
hepatitis B & hepatitis C and alcohol
consumption
# Metastasis : lymph nodes, Lung, bones,
adrenals and brain
# AFP is increased in over 90% of patients
# CEA increase in liver metastasis and of
great value during therapy and follow-up
(92%)
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LUNG CANCER
# There are two major categories of lung
cancer, small cell (SCLC) and non-small
cell (NSCLC) lung carcinomas
# The main risk factor is cigarette
smoking, possibly combined with a
genetic predisposition
# Other risk factors include inhalation of
carcinogens such as asbestos, arsenic,
tar & nickel. Chronic bronchitis possibly
promotes carcinogenesis
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METASTASIS
# 90% Lymphogenic to regional lymph
nodes
# Distant metastases: liver, bones,
adrenals, kidneys & brain
# CYFRA 21-1 is the markers of choice
# CEA can be significantly enhanced CYFRA
21-1 results
# NSE, SCCA and TPS are also used
N.B.
# CYFRA 21-1 = Cytokeratin fragments 21-1
# SCCA = Squamous cell carcinoma antigen
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OVARIAN CANCER
# The most important risk factors are
hormonal imbalance (as in post
menopause) as well as pre-malignant
diseases of the breast & or endometrium
# Metastasis are mainly via the
peritoneum and also to liver, bone &
uterus
# CA125 is the marker of choice
# AFP, HCG, CEA & TPS also are also
used
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PANCREATIC CANCER
# Risk factors include smoking, dietary
habits such as high meat & fat intake,
excessive alcohol, coffee, tea & tobacco
intake as well as chronic pancreatitis
# Metastasis are to regional lymph nodes
and peritoneum while distal metastasis
goes to lungs and liver
# CA19-9 expressed in 82% of pancreatic
adenocarcinoma and together with CEA it
gives better results
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PROSTATE CANCER
# Risk factors include hormonal imbalance &
benign prostate hyperplasias
# Metastasis include: lymphogenic to
regional lymph nodes and haematogenic,
mainly to the skeleton and lung
# For routine measurement and to confirm
diagnosis of prostate cancer, PSA is mainly
used, while PAP although it is a sensitive
marker but is less sensitive than PSA
# PSA, free PSA can be used for differential
diagnosis of the malignant tumor with benign
illness
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BLADDER CANCER
# Bladder carcinoma shows a marked tendency
to recur within the first two years
# The chronic inflammation of the bladder,
aniline derivatives, metabolites of aromatic
amines & nicotine abuse are the most common
risk factors
# Metastasis: early to the regional lymph nodes
then haematogenic metastasis to the liver,
lung, skeleton & peritoneum
# TPA (tissue polypeptide antigen) is the tumor
marker of the choice for bladder carcinoma and
CEA can also used
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UTERINE CANCER
Risk factors
1- 80% of endometrial carcinomas occur
after menopause
2- Long-term estrogen stimulation,
overweight, liver disease, hypertension,
infertility, history of breast, colon or ovarian
carcinomas
# Metastasis occur to regional lymph nodes,
ovaries, vagina or bone
# SCCA, HCG and CEA are used
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Estrogen and progesterone

receptors as tumor markers
# Estrogen and progesterone receptors
are used in breast cancer as indicators
for hormonal therapy
# Patients with positive estrogen and
progesterone receptors tend to respond
to hormonal treatment
# Those with negative receptors will be
treated using other therapies, such as
chemotherapy
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# Patients with positive receptors levels

tend to survive longer, while the disease
is more aggressive in patients with
negative receptors
# The estrogen receptor protein is found
in target tissue cells, such as in the
uterus, pituitary gland, hypothalamus
and breast
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Abbreviations
# CEA :Carcinoembryonic antigen
# FP (AFP): alpha-fetoprotein
# PSA :Prostate specific antigen
# PAP : Prostatic acid phosphatase
# CA125 : Cancer antigen 125
# CA15-3 :Cancer antigen 15-3
# HCG : Human chorionic gonadotropin
# TPA : Tissue polypeptide antigen
# TPS : Tissue polypeptide-specific antigen
# MCA: Mucin-Like carcinoma-associated antigen
# SCLC: Small cell lung carcinomas
# NSCLC: Non-small cell lung carcinomas
# CYFRA 21-1 = Cytokeratin fragments 21-1
# SCCA = Squamous cell carcinoma antigen
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