Tumor Markers

Dr. Marwa Abd El-Haq

Overview
• Cancer is uncontrolled growth of cells that
can spread to other areas of the body.
• The formation (tumorigenesis) & spreading
(metastasis) of tumors are caused by
genetic mutations
• These mutations include activation of
growth factors, inhibition of apoptosis,
tumor suppressor and cell cycle regulation
genes.
 Clinical Aspects
• Early diagnosis is not an easy job as
carcinoma is usually asymptomatic.

• Most diagnostic procedures (e.g. X-ray,

CT, mammography, isotope scanning)
only detect tumor at 1-2 cm size.

• At this time, tumor already consists of

>1 billion cells.
 What are Tumor Markers?
• Substances that can be found in the body
when cancer is present.
• They can be found in the blood in higher
amounts than normal when a certain type
of cancer is present.
• Some are found in urine or other body
fluid, and others are found in tumors and
other tissues.
 Tumor Markers
• They may be made:
1. By the cancer cells themselves
2. or by the body in response to
cancer.
 Ideal Tumor Markers
➢ Tumor-specific
Released only from tumor cells
➢ Type-specific
Elevated in response to one cancer type
➢ High diagnostic sensitivity
Early detection and/or early prediction of
recurrence
➢ High diagnostic specificity
Not elevated in absence of cancer
➢ Concentration reflects tumor size
➢ Predict recurrences before they are clinically
detectable
 Ideal Tumor Markers
• Ideal tumor marker for screening
asymptomatic population should be:
–100% sensitive: always positive in
patients with the disease
–100% specific: always negative in
individuals who do not have the
disease
 Ideal Tumor Markers

• Unfortunately, All of the presently

available tumor markers Do not fit
this ideal model.
 Utility Of Tumor Markers
1. Screening and early detection of cancer
looking for cancer in people who have no
symptoms of the disease
2. Diagnosing cancer:
• Usually, tumor markers are not used to
diagnose cancer
• Cancer can only be diagnosed by a biopsy
 Utility Of Tumor Markers
3. Determining the outlook (prognosis)
for certain cancers
4. Seeing how well treatment is working
5. Detecting recurrent cancer
6. Targeting for therapy (choice and
response)
 When are tumor markers
checked?
• Tumor markers may be checked:
1. At diagnosis
2. Before, during, and after treatment
3. And then regularly for many years to see
if the cancer has come back
 Determination of Tumor
Markers
• Immunochemistry
➢Radio Immune Assay
➢ELISA
➢Immunofluorescence
• Immunohistochemistry: in tissue biopsy
• Immunocytochemistry: in fine needle
cytology
 Classification of tumor
markers
• Oncofetal antigens
• Hormones
• Enzymes
• Tumor-associated antigens
• Special serum proteins
• Miscellaneous markers
 Oncofetal Antigens
Produced during embryonal /fetal
period.

In adults, their production is limited or

completely absent.

Elevated concentrations in adults are

usually connected to malignant process.
 Oncofetal antigens
Produced in E/F gastrointestinal
tract, liver and pancreas.
Elevated in primary colorectal
cancer, GI, breast, lung, ovarian, liver,
CEA prostate and pancreatic cancers.
Used to monitor patients with
colorectal cancer during treatment.

But it is not useful as a screening

or diagnostic test.
 CEA
• Normal serum level < 2.5 ng/ml
• Benign conditions which increase CEA
level:
1. Inflammatory bowel disease
2. Pancreatitis
3. Cirrhosis
4. Chronic obstructive pulmonary diseases
5. Smoking
 Oncofetal antigens
➢Alpha-Fetoprotein (AFP)
• Increased in germ cell tumors (testis and
ovary) and in hepatocellular carcinoma
• Benign causes of increased serum AFP:
1. Pregnancy
2. Obstructive jaundice
3. Hepatitis
4. Cirrhosis
 Hormones
➢Human Chorionic Gonadotropin
• (ß-hCG) one of the most applicable tumor
markers.
• Elevated serum concentrations of hCG can
be found in almost all female patients
having tumors with trophoblastic
component as: choriocarcinomas,
hydatidiform moles, and germ cell ovarian
tumors
• Also in male patients with germ cell
testicular tumors
 Hormones
• Other hormones:
Hormones of malignant endocrine tumors
as:
1. Parathyroid hormone
2. Insulin
3. Calcitonin
 Enzymes
➢Prostatic Acid Phosphatase
• Enzyme produced in normal prostatic
tissue.
• Elevated serum concentrations can be
detected in the patients with prostatic
cancer.
• Measurement of prostatic acid
phosphatase alone does not provide any
clinically useful information additional to
PSA measurement.
 Enzymes
➢Alkaline Phosphatase
• Synthesized in the liver, bones.
• Elevated serum concentrations in patients
with metastatic spread of malignant tumor
into the liver and/or bones,
• And/or the presence of primary bone
tumors (osteosarcoma)
 Tumor-Associated Antigens
• Group of markers that comprises various
membrane structures of tumor cells
✓CA 15-3: monitoring breast CA
• CA 125: monitoring of serous ovarian CA
(response to chemotherapy and
recurrence)
• CA125 is not recommended for screening
asymptomatic women.
✓CA 19-9
• Is widely used as a serum marker for
pancreatic cancer.
• Its use is limited to monitoring response to
therapy, not as a diagnostic marker.
• CA 19-9 levels are also elevated in
patients with other cancers, including
those of the biliary tree, stomach, colon,
liver and lung.
 ✓Prostate Specific Antigen (PSA)
• Is a protease that is formed in the prostatic
epithelium and secreted into the prostatic ducts.
• PSA is also elevated in:
1. Benign prostatic hyperplasia (BPH)
2. Prostatitis
3. Prostatic infarction
Thus, PSA is considered a tissue-specific rather than
a prostate cancer–specific marker
• Increasing PSA specificity for detecting prostate
cancer by measuring free PSA (PSA)
• Total PSA =circulating fPSA+ PSA bound to
alpha-1-antichymotrypsin (PSA-ACT)
• The free fraction constitutes from 5% -> 40% of
the total percent
• Men with benign disease generally present with
higher %fPSA than men with prostate cancer
• PSA is recommended for treatment of patients
with prostate cancer to monitor disease status
after treatment
 Miscellaneous Markers
• Hormone receptors
✓ER&PR
• The primary purpose of determining ER and PR
is to select for likely response to hormonal
therapy in patients with breast cancer.
• In combination with established prognostic
factors (tumor stage, tumor grade, and number
of lymph node metastases), ER and PR may
also be used for determining prognosis in
patients with breast cancer
✓Her-2

• Her-2 is a human epidermal growth factor

receptor.
• It should be measured all patients with invasive
breast cancer.
• The primary purpose of measuring Her-2 is to
select patients with breast cancer that may be
treated with chemotherapy.
✓BRAC 1 and BRCA 2
• BRCA 1 and BRCA 2 mutation testing may be
used for identifying women who are at high risk
of developing breast or ovarian cancer in high-
risk families.
• For those with BRAC mutations, screening
should begin at 25 to 30 years of age.
Drawbacks of tumor markers
• Almost everyone has a small amount of
these markers in their blood, so it’s very
hard to detect early cancers.
• The levels of these markers tend to get
higher than normal only when there’s a
large amount of malignant cells.
• Some people with cancer never have high
tumor marker levels.
• Even when levels of these markers are
high, it doesn’t always mean cancer is
present.
These are the reasons why, today, tumor
markers are used mainly in patients who
have already been diagnosed with cancer
to watch their response to treatment or
look for the return of cancer after
treatment.
Combining of known tumor markers
into marker panels
will help to increase sensitivity and
specificity of diagnostics

MULTIPLE TUMOR MARKERS NEED TO BE OBTAINED

FOR EACH COMMON TYPE OF CANCER

preferably by high-throughput methods

 Summary
• Mainly not for diagnostsis but for
monitoring.
• They can help in the diagnostic process.
• Positive finding of tumor markers is of
important value, but negative finding does
not exclude a malignant tumor!!!
• For diagnosis, histopathological
examination and panel TU markers
determination are decisive.
• Transient elevation of a tumor marker may
occur in non-malignant conditions as
inflammation.