 Definition: a substance produced by a tumor or by a

host in response to the tumor’s presence; such

substances can be measured in blood, fluid
secretions, or tissues by :
 chemical, immunochemical, and molecular
biology methods or by cytochemical staining

 Classifications: markers include enzymes and

isoenzymes, specific proteins, hormones, oncofetal
antigens, carbohydrate epitopes, receptors,
metabolites, and genetic changes
1. To check for recurrence (main use)
2. For screening populations and high-risk groups
3. In staging or confirmation of histopathology
4. In therapy to target the therapy & monitor drug
response
5. As an aid in diagnosis (limited value; lack of
specificity and sensitivity)

NB. Their use is mainly in carcinoma, less so in

sarcoma
1. Screening To identify early cancer risk
2. Surveillance To detect recurrence
3. Staging To assess & stratify the risk
4. Prognosis To predict the outcome
5. Localization To locate the primary
6. Therapy To target the therapy
7. Monitoring To evaluate response to therapy.
8. Diagnosis To corroborate the diagnosis
1. Cancer heterogeneity
2. Lack of Specificity – false positives
3. Lack of Sensitivity - false negatives
4. Benign diseases - positive CA 125 or CEA
5. Smokers have raised CEA
6. Normal persons also have small amounts
7. Higher levels only with large tumor volume
8. Some cancers never have higher levels
 Glycoprotein, found in fetal liver, yolk sac, GI
tract.
 half-life：4~6 days
 Normal serum levels：
 12~15th gestational w 30~40 ng/ml
 At birth 30 ng/ml
 >1 years old <20 ng
Increased in:
1. Primary hepatocellular cancer (AFP levels ≥200 and 400
ng/mL in patients with an identifiable liver mass by imaging
techniques are diagnostic of hepatocellular carcinoma with
high specificity).

1. Nonseminomatous germ cell tumors of the ovary

and testis (eg, yolk sac and embryonal carcinoma).
 Normal：<37 u/ml.
 Mainly for pancreatic adenocarcinoma.
 Rarelyelevated in patients with benign
disease such as pancreatitis, hepatitis and
cirrhosis.
 Cut-off: 60 U/mL
dis Cut-off: 37 U/mL

20.3% (14/69) 8.9% (6/69)

Pancreatitis

16.3% (7/43) 9.3% (4/43)

Hepatitis

30.5% (18/59) 6.8% (4/59)

Cirrhosis

Pancreatic
cancer 75.9% (63/83) 73.2% (60/82)
 Tumor-associated glycoprotein.
 The normal value is less than 35 U /ml.
 Increased in most patients with epithelial
ovarian cancers.
 Should be used as an aid in the detection of
residual ovarian cancer in patients who have
undergone first-line therapy.
 4/Carcinoembryonic antigen (CEA)

 Glycoprotein.
 Elevated CEA levels are found predominantly in
colorectal cancer and also in
 Pancreatic cancer, cervix cancer, lung cancer,
ovarian cancer, breast cancer, and urinary tract
 CEA is the preferred test for patients with colorectal
cancer
 CA 19-9 is the preferred test for patients with
pancreatic cancer.
 The combination of CA 19-9 with CEA increases the
sensitivity for detection of recurrence of gastric
cancer to 94%.
CEA--Gastric Cancer --59%
CA 19-9--Gastric Cancer--79%
 Useful for
 identifying hormone-dependent tumors
 prognostic markers.
 Identifies those patients who will respond to hormone
therapy and those who will need more aggressive
treatment.
 If ER and PR are both positive, there should be a
better response to hormone therapy.
 ER-positive tumors have been associated with
longer disease-free interval for the patient and
possibly longer survival.
 Her2/neu is human epidermal growth factor receptor.
 Her2/neu is used to Identifies those patients with
breast tumors that will respond to:
 Chemotherapy.
 Herceptin (trastuzumab) is a humanized monoclonal
antibody that binds to Her2/neu and inhibits
activation of the receptor, consequently breast
tissue that is positive for Her2/neu are candidates
for Herceptin therapy. Currently the test is best
performed on breast tissue biopsy specimens.
 A glycoprotein hormone consisting of an α- and β-chain.
Increased in pregnancy with peak between 8th and 12th week of
gestation

 Human chorionic gonadotropin can be used as a

tumor marker, as its β subunit is secreted by some
trophoblastic cancers including seminoma, choriocarcinoma,
germ cell tumors, hydatidiform mole formation, teratoma with elements
of choriocarcinoma, and islet cell tumor.

 hCG Combined with other tests such as AFP and

lactase dehydrogenase, to help diagnose germ
cell tumors
 Prostatic acid phosphatase (PAP), is an enzyme
produced by the prostate. It may be found in
increased amounts in men who have prostate
cancer or other diseases.
 Elevated levels following treatment may indicate
residual or recurrent disease.
 Test has relatively low sensetivity.
 Increased in prostatic cancer but also in benign
prostatic hypertrophy (BPH).

 Increasing the cut-off point to 10 μg/L reduces

positive results of malignancy from BPH to <2-3%.

 PSA exists in the free form and bound to proteins

like α1-antichymotrypsin. Measurement of the
ratio of free to total PSA may have advantages in
the differential diagnosis of BPH from malignancy
(high total PSA &lower percentage of free PSA are associated with
higher risks of prostate cancer).
 PAP Positivity PSA Positivity

BPH 3% 63%

Stage A 0% 52%

Stage B 8% 78%

Stage C 60% 100%

Stage D 90% 100%

 Exact figures may differ somewhat
between studies, but in principle, there
is agreement. PAP is less sensitive than
PSA, but it is more specific.
 A glycoprotein and subfraction of a tumor-
associated antigen (TAA).
 Increased levels are associated with tumor
progression or recurrence in cervical and
uterine squamous cell cancer.
 Useful for monitoring clinical management.
 Elevated in lymphoblastic leukemia and undifferentiated
leukemia and in chronic myelogenous leukemia in blast
crisis.

 Considered to be a biochemical marker for certain

immature lymphocytes.

 Levels may increase and decrease as certain leukemia

patients remit and relapse.

 May be helpful in the classification of leukemia and in

selection and monitoring of therapy.
 The associated antigen is a human complement factor
H related protein (hCFHrp).
 The BTA test is a single step immunochromatographic
assay for bladder associated antigen in voided urine.
 The clinical specificity of the test is 95.9% and clinical
sensitivity 40-59%.
 The test is superior to the voided urinary cytology in
the detection of recurrent bladder cancer. It will
reduce, but not eliminate, the use of cystoscopy.
1. Alpha fetoprotein antigen (AFP) in hepatoma
2. Carcino-Embryoinic Antigen (CEA) in GI tumors
3. Cancer Antigen 125 (CA 125) in ovarian carcinoma
4. Cancer Antigen 15-3 (CA15-3) in breast cancer
5. Cancer Antigen 19-9 in pancreatic tumor
6. Prostatic specific antigen (PSA) - prostatic tumors