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

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,

THANK YOU