tumor markers: clinical usefulness by amr s. moustafa, m.d.; ph.d
Post on 25-Dec-2015
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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?
Common Tumor Markers
Alpha-fetoprotein
CEA
CA-19.9
PSA
CA-125
-hCG
VMA
CA-15.3
Estrogen receptor
Progesterone receptor
HER-2/NEU
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 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 cancerTreatment 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 receptorsIf 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 19-9CEA
5. Colorectal carcinoma CEACA 19-9
6. Pheochromocytoma Vanillylmandelic Acid (VMA) in urine
7. Nonseminomatous testicular cancer
AFP-hCGCEA
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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