Download Tumor Markers

Tumor Markers
Lecture two
By
Dr. Reem Sallam
Objectives
 To briefly enumerate the most commonly
used methods to test for tumor markers
 To describe examples of the most
commonly ordered tumor markers, their
regulation and physiology, their clinical
application and interpretation, and their
pathophysiology
 To be familiar with the most common tumor
marker used in various cancers.
 To be able to choose a tumor marker (or
markers) in examples of clinical situation.
Lecture outlines
 Examples of methods used to
measure tumor markers
 Examples of tumor markers
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Alpha-fetoprotein
CA125
CEA
hCG
PSA
Others
Examples of methods used to
measure tumor markers
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Immunoassays
HPLC
Immunohistochemistry
Enzyme assays
Examples of Frequently ordered
tumor markers
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Alpha-fetoprotein
CA-125
CEA
hCG
PSA
Her-2/neu
P53
BrCa1
BrAa2
CA-15.3
CS-19.9
Estrogen and progesterone receptor
VMA
Alpha feto protein (-FP)
 Introduction & Description:
 AFP is an abundant serum protein
normally synthesized by the fetal liver
that is reexpressed in certain types of
tumors. i.e. it is a carcinoembryonic
protein (or oncofetal antigen)
AFP continued…
 Clinical Application & Interpretation:
 Used for the diagnosis, staging,
prognosis, and treatment monitoring of
hepatocellular carcinoma (HCC; i.e.
hepatoma).
 However, AFP is not completely specific
for HCC.
 AFP might be increased in pregnancy &
benign liver disease.
AFP continued…
 Several expert groups now recommend that
AFP be used in conjunction with ultrasound
imaging every 6 months in patients at high
risk of developing HCC.
 This includes patients with hepatitis B
virus- and/or hepatitis C virus-induced liver
cirrhosis.
 i.e. AFP is used for early detection (in the
lead period) which is ~ 6 months before
clinical manifestations of the cancer appear.
AFP continued…
 AFP is also used as a tumor marker
for classification and monitoring
therapy for nonseminomatous
testicular cancer.
 This is in combination with another
tumor marker: -human chorionic
gonadotropin (-hCG)
Cancer Antigen 125 (CA-125)
 Introduction and Description:
 CA-125 may be useful for detecting
ovarian tumors at an early stage and for
monitoring treatments without surgical
restaging
 CA-125 is not considered specific enough
for ovarian cancer, as it may be elevated
in patients with endometriosis, during
the first trimester of pregnancy, or
during menstruation.
CA-125, continued…
 Clinical application and interpretation:
 CA-125 is the only clinically accepted
serologic marker of ovarian cancer.
CA-125, continued…
 Application and Pathophysiology:
 CA-125 is predominantly used to monitor
therapy and to distinguish benign
masses from ovarian cancer.
Carcinoembryonic Antigen (CEA)
 Introduction and Description:
 CEA is an example of an oncofetal
antigen
 It is expressed druing development and
then reexpressed in tumors.
 It is the most widely used tumor marker
for colorectal cancer.
CEA, continued…
 Clinical Application and
Interpretation:
 The main clinical use of CEA is as a
tumor marker for colorectal cancer
 In colon cancer, CEA is used for
prognosis, in postsurgery surveillance
and to monitor response to
chemotherapy.
Human Chorionic Gonadotropin
(hCG)
 Introduction and Description:
 hCG is a hormone normally secreted by
trophoblasts in the placenta during
pregnancy.
 It is a glycoprotein consisting of  and 
subunits.
hCG, continued…
 Clinical Application and
Interpretation:
 It is the most useful marker for detection
of gestational trophoblastic diseases
(GTDs)
 GTDs include:
 Hydatiform mole (vesicular mole)
 Choriocarcinoma
 It is also elevated in nonseminomas.
Prostate Specific Antigen (PSA)
 Introduction and Description:
 PSA is a glycoprotein produced only in
the epithelial cells of the acini and ducts
of the prostatic ducts in the prostate.
 PSA is a serine protease.
PSA, continued…
 Regulation and Physiology:
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There are 2 major forms of PSA that are found
circulating in the blood:
 Free
 Complexed:
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Complexed to 1-antichymotrypsin or 2-macroglobulin.
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The detection of total PSA has been used in screening
for and in monitoring of prostate cancer
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The measurement of free PSA can help to differentiate
levels of PSA that are in the grey zone: i.e. not high
enough to diagnose cancer prostate, but not low enough
to rule out the diagnosis of cancer prostate: Patient with
cancer prostate have a lower % of free PSA.
PSA, continued…
 Clinical Application and
Interpretation:
 Annual PSA testing for screening of
prostate cancer:
 in men over 50 years old
 in younger men at high risk: e.g.
 Those with a family history of prostate
cancer.
PSA, continued…
 To increase the accuracy of the PSA
testing, it is essential to use ageadjusted cutoff values of PSA
 Reasons other than prostate cancer that
can  elevated PSA:
 Prostate infection
 Prostate irritation
 Benign prostatic hyperplasia (enlargement)
PSA, continued…
 Application & Pathophysiology:
 The best clinical use & first clinical
applications of PSA testing was to
monitor for the progression of
prostate cancer after therapy (e.g.
radical prostatectomy)
Common Cancer Terms
Angiogenesis
Development of new blood vessels to supply oxygen and
nutrients to cells
Physiological
The process is transient
and regulated
e.g. Wound healing,
Pregnancy,
Menestruation,
development
Pathological
The process is persistent and out of
regulation (out of control)
e.g. tumorogenesis
Example of marker for angiogenesis:
Vascular Endothelial Growth Factor (VEGF)
Application: treatment that can target
more than one tumor (because it will cut the
blood supply from the tumor, i.e.
nonspecific)
Her-2/neu
 It is a proto-oncogene that upon:
 Mutation (especially point mutation) or
 Altered (over) expression
will encode an Epidermal Factor Receptor (EGF-R) that
mediate tumorigenesis (i.e. It is an activation
mutation)
 Marker for breast and ovarian cancers
 Application: It is now routinely measured in breast
cancer to determine the type of therapy:
 Breast cancer positive for Her-2/neu is responsive
to treatment (Herceptin)
 Breast cancer negative for Her-2/neu is NOT
responsive to treatment
Tumor suppressor genes, e.g. p53
Tumor
suppressor gene
Encodes a protein involved in protecting cells from
unregulated growth
•The gene is located on chromosome 17 (together with
the genes of BrCa1 and Her-2/neu
•Encodes a protein of 53 kDa
•Encodes a protein that normally result in cell cycle arrest
and induces apoptosis
•Upon mutation: loss of function mutation  cancer
Suggested Recommended Markers for
diagnosis/prognosis
Tumor
Tumor markers
1. Hepatoma
(HCC)
AFP
2. Cancer
ovary
 CA-125
 Inherited ovarian cancer: BrCa1(on
chromosome 17, which is the same
chromosome having the p53 & Her-2/Neu)
3. Breast
Cancer
 CA15-3
 CEA
 Her-2/neu
 Estrogen and progesterone receptors
 If inherited: BrCa1, and BrCa2 (on
chromosome 13)
Suggested Recommended Markers for
diagnosis/prognosis, continued
Tumor
Tumor markers
4. Cancer head of the pancreas
CA 19-9
CEA
5. Colorectal carcinoma
CA 19-9
CEA
6. Pheochromocytoma
Vanillylmandelic
Acid (VMA) in urine
7. Nonseminomatous testicular cancer
AFP
-hCG
CEA
8. Vesicular mole and Choriocarcinoma -hCG
9. Prostate cancer
PSA
Tools for early detection of cancer
 Find a marker that will be detected in
the lead time (~ 6 months before
clinically detected)
 Use prognostic markers for cancer
progression
 Find targets for new therapeutic
application
 Follow up the treatment
Case study:
 A 50 years old female suffered from cancer breast 5
years ago, and underwent radical surgical procedure.
She did not have any family history for cancer breast.
Recently, metastases were detected in her liver. Which
one of the following tumor markers is the best for
diagnosis, prognosis, & monitoring therapeutic
intervention of this case?
 BrCa1
 BrCa2
 Alpha feto protein (AFP)
 CA 15-3
Case study:
 A 50 years old female suffered from cancer breast 5
years ago, and underwent radical surgical procedure.
She did not have any family history for cancer breast.
Recently, metastases were detected in her liver. Which
one of the following tumor markers is the best for
diagnosis, prognosis, & monitoring therapeutic
intervention of this case?
 BrCa1
 BrCa2
 Alpha feto protein (AFP)
 CA 15-3
Things to remember
 No ideal tumor marker is known so
far
 Therefore, the best approach is:
 Take a good history
 Perform thorough physical examination.
 Use a battery of markers (>1
marker/tumor)
 Use confirmatory investigations:
Histopathology, ultrasonography, per
rectal examination, x rays
THANK YOU 