Tumor Markers

Dr. Ahmad Alkhawaldeh

Overview

• Although it is often specified as a single disorder,

cancer is a broad term used to describe > 200 different
diseases that affect > 50 tissues
Estimated new cases of cancer and deaths
from cancer in USA
Male Female

Tissue Incidence Death Tissue Incidence Death

Prostate 29% 9% Breast 26% 15%

Lung 15% 31% Lung 15% 26%

Colorectal 10% 9% Colorectal 11% 10%

Inherited : Expression of inherited oncogene
e.g. viral gene incorporated into host gene
Viral: Human papilloma, herpes type 2, HBV, EBV (DNA) ‐
Human T‐cell leukemia virus (RNA)
Chemical:
‐ Poly cyclic hydrocarbons cause sarcomas
‐ Aromatic amines cause mammary carcinoma
Radiological: Ultraviolet & ionizing irradiation
Spontaneous: Failure in cellular growth control
• Cancer severity is generally classified by a combination of several factors.
• Depending on the type of cancer, these factors include:
– Tumor size
– Histology
– Regional lymph node involvement
– The presence of metastasis
• For most solid tumors (e.g., breast, lung, kidney), cancer is broadly classified (using roman
numerals I‐IV) into 4 stages:
– stage I: Localized primary tumor
– Stage IV: Metastasis and invasion of tumor to distant tissues
• Biological substances synthesized and released by
cancer cells themselves
• Produced by the host in response to the presence of
tumor
• Most tumor markers are proteins
• Detected in a solid tumor, in circulating tumor cells in
peripheral blood, in serum, lymph nodes, in bone marrow,
or in other body fluid (urine, stool, ascites)
 Types of Tumor Markers
• Cancer can be detected and monitored using biologic tumor markers.
• Tumor markers are produced either directly by the tumor or as an effect of the
tumor on healthy tissue (host).
• Tumor markers encompass an array of diverse molecules such as:
– Serum proteins
– Oncofetal antigens
– Hormones
– Metabolites
– Receptors
– Enzymes
 Applications of Tumor Marker Detection
• Ideally, a tumor marker would be:
1. tumor specific
2. absent in healthy individuals
3. readily detectable in body fluids.
• Unfortunately, all of the presently available tumor markers do
not fit this ideal model.
• However, a host of tumor markers have been identified that have
a high enough specificity & sensitivity to be used in:
1. screening populations at risk & diagnosis
2. Prognosis
3. Detection of recurrence & monitoring response to
treatment.
 Early
Screening
Detection

Diagnosis Monitor
1. Screening To identify early cancer risk
2. Diagnosis To corroborate the diagnosis
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. Surveillance To detect recurrence in F‐Up
8. Monitoring To evaluate response to Rx.
 Sensitivity and Specificity

• Ideal tumor marker for screening asymptomatic

population should be:
– 100% sensitive: Always positive in patients with the
disease
– 100% specific: Always negative in individuals who do not
have the disease
 Examples of sensitivity & specificity

• If a test gives positive results in 199 patients out of

200 patients: its sensitivity is 99.5%
• If a test gives negative results in 90 normal individuals
out of 100 normal individuals: its specificity is 90%
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
Antigens Hormones

TUMOR

Enzymes Tissue Specific

1. Viral Antigen :
a‐ Viral proteins and glycoproteins
b‐ New antigens produced by virally infected
host cells under control of viral nucleic acid
2. Tumor specific antigens :
‐ Tumor cells develop new antigens specific to
their carcinogens
3. Tumor specific transplantation antigens :
‐ Tumor cells express new MHC antigens due to
alteration of normally present MHC antigens
4. Oncofetal antigens:
a‐ Carcino‐embryonic antigens (CEA)
‐ Normally expressed during fetal life on fetal gut
‐ Reappearance in adult life:
GIT, pancreas, biliary system and cancer breast
b‐ Alpha fetoprotein:
‐ Normally expressed in fetal life
‐ Reappearance in adult life; hepatoma
A. Hormones :
Human Chorionic Gonadotrophins (HCG) are secreted in
Choriocarcinoma, Ovarian Ca;
Thyroxin is secreted in thyroid cancer
B. Enzymes :
Acid phosphatase in prostate cancer; Alkaline
phosphatase, lipase and amylase enzymes in cases of
cancer of pancreas
• Prostate Specific Antigen(PSA) is a glycoprotein
• Ideal as a tumor marker, high tissue specificity
• High sensitivity for prostate cancer
• Also elevated in BPH & prostatitis
• Useful in
– Dx. & follow up of prostate Ca, Prognostic factor
– To monitor recurrence & response to treatment
– An ↑in ratio of free/total PSA is associated with increased
probability of prostate cancer
– 97% specificity, 96% sensitivity for prostate Ca
– For population screening and diagnosis an increase of 0.75
ng/ml per year in any given patient has high sensitivity and
specificity for prostate cancer vs BPH,
• Elevated in Ovarian, Endometrial, Pancreatic, Lung,
Breast, Colon cancers and also in
• Menstruation, Pregnancy, Endometriosis and other
gynecological and non gynec conditions.
• Useful in monitoring ovarian Ca recurrence & Rx.
– Cell surface glycoprotein, present during embryonic
development of coelomic epithelium & is present in
adult structures derived from it
– For follow up, an increase may predict recurrent
disease, precedes clinical recurrence by months
– >80% of epithelial ovarian cancer.
– Correlates with tumor bulk,
– In Endometriosis most common
• Alfa Feto Protein is a serum fetal protein synthesized by the liver,
yolk sac, gastrointestinal tract – a glycoprotein
• In Hepatocellular Cancer: It is useful for diagnostic and also useful
for screening of high risk population (HBV, HCV)
• Benign conditions: hepatic parenchymal inflammation, hepatic
necrosis, pregnancy, primary biliary cirrhosis, extra hepatic
biliary obstruction give positive test.
• Diagnosis, Prognosis, to monitor recurrence & response
• The absolute AFP level correlates with tumor bulk
• Cancers of pancreas, colon, stomach & bronchogenic Ca
• Complex glycoprotein that is associated with the plasma
membrane of tumor cells, from which it may be
released in to the blood
• Elevated specially in Colon cancer, Adeno. Ca uterus
• Normal pre Rx CEA indicates no metastasis
• Also in Pancreatic, Gastric, Lung, breast & Ovarian Ca
• Also in cirrhosis, inflammatory bowel disease, chronic lung
disease, pancreatitis, fibrocystic breast disease
• Not satisfactory for screening for a healthy population
• Good for monitoring recurrence & to monitor Rx.
• In 21‐42% patients of gastric Ca
• In 20‐40% patients of colonic Ca
• In 71‐93% patients of pancreatic Ca
• For DD of benign from malignant disease
• Dx, FU, Relapse, 70% specificity & 90% sensitivity
• Human chorionic gonodotropin (βHCG)
– Glycoprotein synthesized by trophoblastic cells of normal
placenta
– Serum and urine HCG ↑ in early gestation and peak in the first
trimester (60~90 days)
– Elevated in Gestational trophoblastic disease (a progressive
rise in after 90 days of gestation → highly suggestive),
choriocarcinoma
– Elevated in testicular cancer
– Monitor treatment response, relapse & recurrence
1. Alpha fetoprotein antigen (AFP) in hepatoma
2. Carcino‐Embryoinic Antigen (CEA) in GI tumors
3. CEA in tumors of biliary system and cancer breast
4. Cancer Antigen 125 (CA 125) in ovarian carcinoma
5. Cancer Antigen 15‐3 (CA15‐3) in breast cancer
6. Cancer Antigen 19‐9 in colon and pancreatic tumor
7. Prostatic specific antigen (PSA) ‐ prostatic tumors