Tumor Markers: Clinical Usefulness

1. Tumor Markers: Clinical Usefulness By 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 • CA-15.3 • Estrogen receptor • Progesterone receptor • HER-2/NEU • BRCA1 • BRCA2 • p53 • Alpha-fetoprotein • CEA • CA-19.9 • PSA • CA-125 • -hCG • VMA

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 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 • 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 • 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

23. Recommended Tumor Markers for Specific type of Cancers….continued

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,

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