Transcript Tumor Markers: Clinical Usefulness

Tumor Markers: Clinical Usefulness
By
Amr S. Moustafa, M.D.; Ph.D.
Objectives
 The most commonly used methods for the
detection of tumor markers
 When to use tumor markers in various
cancers?
 What tumor marker (or markers) to
order in different cancers?
Tumor markers: Detection
 Immunoassays
 Immunohistochemistry
 FISH
 Enzyme assays
 HPLC
Common Tumor Markers
 Alpha-fetoprotein
 CA-15.3
 CEA
 Estrogen receptor
 CA-19.9
 Progesterone receptor
 HER-2/NEU
 PSA
 CA-125
 -hCG
 VMA
 BRCA1
 BRCA2
 p53
Alpha feto protein (-FP)
 Introduction:
 Oncofetal antigen
 Abundant serum protein normally
synthesized by the fetal liver
 Re-expressed in certain types of
tumors
AFP continued…
 Clinical Applications:
 Diagnosis, prognosis, and treatment
monitoring of hepatocellular carcinoma
(HCC; hepatoma)
 Screening (High-risk; HBV or HCV patients)
 AFP is not completely specific for HCC
 AFP might be increased in pregnancy &
benign liver disease
AFP continued…
 AFP be used in conjunction with
ultrasound every 6 months in patients
at high risk of developing HCC
 Patients with hepatitis B virus- and/or
hepatitis C virus-induced liver cirrhosis
 Lead period i.e., early detection which
is ~ 6 months before clinical
manifestations
AFP continued…
 A tumor marker for classification
and monitoring therapy for
nonseminomatous testicular
cancer
“in combination with -human
chorionic gonadotropin (-hCG)”
Cancer Antigen 125 (CA-125)
 Detection of ovarian tumors at an
early stage
 monitoring treatments without
surgical restaging
 CA-125 is not specific for ovarian
cancer, as it may be elevated in:
 Menstruation
 First trimester of pregnancy
 Endometriosis
CA-125, continued…
 Currently, CA-125 is the only
clinically accepted serologic
marker of ovarian cancer
Carcinoembryonic Antigen (CEA)
 Introduction:
 CEA is an oncofetal antigen
 It is expressed druing development
and then re-expressed in tumors
 It is the most widely used tumor
marker for colorectal cancer
CEA, continued…
 Clinical Applications:
 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:
 hCG is a hormone normally secreted
by trophoblasts in the placenta
during pregnancy
 It is a glycoprotein consisting of and -subunits
hCG, continued…
 Clinical Applications:
 Detection and follow-up of gestational
trophoblastic diseases (GTDs)
 GTDs include:
 Hydatiform mole (vesicular mole)
 Choriocarcinoma
 It is also elevated in nonseminomas
testicular cancers
Prostate Specific Antigen (PSA)
 Introduction:
 PSA is a glycoprotein produced by
the epithelial cells of the acini and
ducts of the prostatic ducts in the
prostate
 PSA is a serine protease
PSA, continued…
 There are 2 major circulating
forms of PSA:
Free
Complexed:
 Complexed to 1-antichymotrypsin
or 2-macroglobulin
PSA, continued…
 Annual PSA 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
 Total PSA: Screening for and in
monitoring of prostate cancer
 Free PSA:
 Differentiate levels of PSA that are in the grey
zone
 Patient with cancer prostate have a lower %
of free PSA
PSA, continued…
 To increase the accuracy of the PSA
testing, age-adjusted cutoff values
of PSA can be used
 Elevated PSA can be found also in:
 Prostate infection
 Pelvic congestion
 Benign prostatic hyperplasia
(enlargement)
Common Cancer Terms
Angiogenesis
Development of new blood vessels to supply
oxygen and nutrients to cells
Physiological
The process is transient
and tightly regulated
Pathological
The process is persistent and out of
control
e.g., Wound healing,
e.g., tumorogenesis & Metastasis
Pregnancy, Menstruation,
Marker for angiogenesis: e.g., Vascular
development
Endothelial Growth Factor (VEGF)
 Follow-up & treatment of angiogenic
cancer
 Treatment can target more than one
tumor type
HER-2/NEU

Encodes an Epidermal Growth Factor Receptor (EGF-R)

A proto-oncogene that is converted to oncogene by:
 Mutation (especially point mutation) or
 Altered (over) expression

Marker for breast and ovarian cancers

It is now routinely measured in breast cancer (IHC and
FISH) to determine the type of therapy:
 Breast cancer positive for HER-2/NEU is
responsive to treatment (Herceptin)
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 (Plus
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
Recommended Tumor Markers for
Specific type of Cancers
Tumor
Tumor markers
1. Hepatoma
(HCC)
AFP
2. Ovarian
Cancer
 CA-125
 Inherited ovarian cancer: BRCA1
3. Breast
Cancer
 CA15-3
 CEA
 HER-2/NEU
 Estrogen and progesterone receptors
 If inherited: BRCA1, and BRCA2 (on
chromosome 13)
Recommended Tumor Markers for
Specific type of Cancers….continued
Tumor
Tumor
markers
4. Cancer head of the pancreas
CA 19-9
CEA
5. Colorectal carcinoma
CEA
CA 19-9
6. Pheochromocytoma
Vanillylmandel
ic Acid (VMA)
in urine
7. Nonseminomatous testicular
cancer
AFP
-hCG
CEA
8. Vesicular mole & Choriocarcinoma
-hCG
9. Prostate cancer
PSA
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, liver metastases were suspected. Which one
of the following tumor markers is the best marker for
follow-up 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, liver metastases were suspected. Which one
of the following tumor markers is the best marker for
follow-up 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,
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