Tumour markers are substances that are produced by tumour cells or the body's response to tumours that can be detected and measured in blood, urine, or body tissues. They can be used for screening, diagnosis, staging, detecting recurrence, and monitoring treatment response. However, tumour markers have limitations as they are not always tumour-specific and levels can be elevated in benign conditions. The main uses of common tumour markers are monitoring disease in patients with known cancers like CEA for colorectal cancer, PSA for prostate cancer, and AFP and HCG for germ cell tumours.

1. TUMOUR MARKERS

2. What is a tumour marker?
Almost anything that forms part of a malignant
cell or that is produced by that cell may, in
certain situations, be useful as a tumour marker:
• structural molecules
• secretion products and enzymes
• non-specific markers of cell turnover
ALL HAVE COUNTERPARTS IN NON-MALIGNANT CELLS
How do we use tumour markers?
• Screening/early detection
• Diagnosis/case finding
• Staging/prognosis
• Detecting recurrence
• Monitoring therapy

3. What are the characteristics of
an ideal tumour marker?
• Detectable only if tumour is present
• Identifies the type of tumour
• Circulating concentration correlates with the
mass of tumour present
• Responds rapidly to treatment-induced
remission
• Responds rapidly to relapse
• Should predict outcome
• In patients with stable disease

4. Carcinoembryonic antigen (CEA)
• CEA is a highly glycosylated cell surface glycoprotein involved in intercellular
adhesion
• CEA is shed from the cell surface into the circulation and can be detected in
serum.
• It is thought that infiltrating tumour growth breaks down the normal
barriers that usually prevent CEA from entering the circulation.
Malignancies associated with
elevated CEA levels
Over-expressed primarily by
adenocarcinomas:
 Colon
 Rectum
 Breast
 Lung
Benign conditions associated with
elevated CEA levels
 Pulmonary emphysema
 Bronchitis
 Acute ulcerative colitis
 Rectal polyps
 Hepatitis
 Alcoholic cirrhosis
 Obstructive jaundice
 Smokers
 Renal disease

5. CEA
 Normal range: <5ng/ml
 Smokers: <10ng/ml
 Suspect malignancy at >20ng/ml
 Suspect metastatic spread at >50ng/ml
 T1/2: 3 days (1-5 days)
Dukes’ Grade % patients
CEA >5ng/ml
A 4
B 26
C 44
D 65

6. Cancer Antigen 125 (CA125)
 Glycoprotein, with unknown biological function
 Marker developed through immunization of mice with cells
from an ovarian carcinoma line, to produce the OC 125
monoclonal antibody
Epithelial cells
• Fallopian tubes
• Endometrium
• Endocervix
• Normal ovary
Mesothelial cells
• Pleura
• Pericardium
• Peritoneum

7. ‘Normal’ serum concentration: <35 kU/L
Elevated in menstruation
T1/2: 5 days (1-5 days)
CA125
Malignancies associated with elevated CA 125
80-85% ovarian serous adenocarcinomas
50% Stage I
>90% Stage II
Breast Cervix Endometrium
Uterus Fallopian tubes
Liver Biliary tract
Stomach Colon
Pancreas Lung

10. CA19-9
Normal serum concentration <37 U/ml
T1/2 : 24 hrs
20% patients
with pancreatic
adenocarcinoma
do not produce
CA19-9

12. Prostatic Specific Antigen (PSA)
 Serine protease
 Liquefy seminal coagulum
 Production is androgen-dependent
 Produced almost exclusively by epithelial component
of prostate gland
 Raised in:
Benign prostatic hypertrophy
Acute and chronic prostatitis
Urinary retention
 T½ = 2.5 days (radical prostatectomy)

18. Alpha–fetoprotein (AFP)
 Glycoprotein
 Performs some of the functions of albumin in the
foetal circulation
 Adult normal values <10 U/L
 T1/2 = 5 days
Physiological conditions with elevated AFP
 Pregnancy
 Age <1 year (adult levels achieved between 6 months
and 1 year)

22. Human Chorionic Gonadotropin (βhCG)
 Multiple forms in serum (intact heterodimer, free alpha, free
beta chains, various degradation products)
 Function is to maintain progesterone production during first
2 weeks of pregnancy
Reference: <5 U/L
T1/2 = 16-24 hours
May be biphasic, second T1/2 = 12.8 days
Elevated βhCG:
 Physiological condition: pregnancy
 Benign condition: pituitary adenoma
 Malignancies:
 Gestational trophoblastic disease
 NSGCT
 SGCT testis (20%)

23. Serum Tumour Markers -
Summary
• Tumour markers can contribute to patient management but be
aware of their limitations
• The main application of tumour markers is in monitoring of disease
response to treatment
• Measurement of α-fetoprotein and human chorionic
gonadotrophin is mandatory in the management of germ cell
tumours
• Carcinoembryonic antigen (CEA) is recommended for postoperative
follow-up of patients with stage II and III colorectal cancer

24. Serum Tumour Markers -
Summary
• Prostate specific antigen (PSA) may be used for detecting disease
recurrence and monitoring treatment in patients with prostate
cancer
• In some high risk patients, measurement of α-fetoprotein, CA125,
or CA19-9 may aid early detection of primary liver (hepatocellular)
cancer, ovarian cancer, or pancreatic cancer respectively
• Opportunistic screening with panels of tumour markers is not
helpful
• Measurement of CA125 in men or PSA in women is inappropriate