1. Tumor Markers: Clinical UsefulnessBy
Amr S. Moustafa, M.D.; Ph.D.

2. 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?

3. Tumor markers: Detection
Immunoassays
Immunohistochemistry
FISH
Enzyme assays
HPLC

4. Common Tumor Markers -hCG Alpha-fetoprotein CEA CA-19.9 PSA CA-125
VMA
CA-15.3
Estrogen receptor
Progesterone receptor
HER-2/NEU
BRCA1
BRCA2
p53

5. Alpha feto protein (-FP)
Introduction:
Oncofetal antigen
Abundant serum protein normally synthesized by the fetal liver
Re-expressed in certain types of tumors

6. 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

7. 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

8. AFP continued…
A tumor marker for classification and monitoring therapy for nonseminomatous testicular cancer
“in combination with -human chorionic gonadotropin (-hCG)”

9. 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

10. CA-125, continued…
Currently, CA-125 is the only clinically accepted serologic marker of ovarian cancer

11. 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

12. 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

13. 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

14. 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

15. 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

16. PSA, continued… There are 2 major circulating forms of PSA: Free
Complexed:
Complexed to 1-antichymotrypsin or 2-macroglobulin

17. 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

18. 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)

19. Common Cancer Terms Physiological Pathological
Angiogenesis
Development of new blood vessels to supply oxygen and nutrients to cells
Physiological
Pathological
The process is transient and tightly regulated
e.g., Wound healing, Pregnancy, Menstruation, development
The process is persistent and out of control
e.g., tumorogenesis & Metastasis
Marker for angiogenesis: e.g., Vascular Endothelial Growth Factor (VEGF)
Follow-up & treatment of angiogenic cancer
Treatment can target more than one tumor type

20. HER-2/NEU Mutation (especially point mutation) or
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)

21. Tumor suppressor genes, e.g., p53
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

22. Recommended Tumor Markers for Specific type of Cancers
Hepatoma (HCC)
AFP
Ovarian Cancer
CA-125
Inherited ovarian cancer: BRCA1
Breast Cancer
CA15-3
CEA
HER-2/NEU
Estrogen and progesterone receptors
If inherited: BRCA1, and BRCA2 (on chromosome 13)

23. Recommended Tumor Markers for Specific type of Cancers….continued
Cancer head of the pancreas
CA 19-9
CEA
Colorectal carcinoma
Pheochromocytoma
Vanillylmandelic Acid (VMA) in urine
Nonseminomatous testicular cancer
AFP
-hCG
Vesicular mole & Choriocarcinoma
Prostate cancer
PSA

24. 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

25. 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

26. 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,

27. THANK YOU