Tumor Markers Guide

Tumor Markers
dr. Hendy Wijaya, M. Biomed

Introduction
Descriptions
Ideal Tumor Markers
Usage
Advantages and Disadvantages
Hendy Wijaya, MD, M. Biomed 2

Descriptions
• Tumor markers are biochemical indicators of presence of a tumor  it refers to a molecule

that can be detected in plasma and body fluids
• These markers are either produced by tumor cells (tumor-derived) or by the body in response
to tumor cell (tumor-associated)
• Tumor markers are NOT the primary modalities for cancer diagnosis rather they can be
used as laboratory test to support the diagnosis
Nagpal, M., Singh, S., Singh, P., Chauhan, P., & Zaidi, M. A. 2016. Tumor Markers: A Diagnostic
Tools. National Journal of Maxillofacial Surgery, 7(1): 17-20.
Descriptions
• Cancer is a cluster of diseases involving:

1. alterations in the status and expression of multiple genes that confer a survival advantage
2. undiminished proliferative potential to somatic or germinal cells.
• Alterations primarily in three main classes of genes, namely:

1. (proto) oncogenes, contribute to the development of cancer genotype and phenotype
2. tumor suppressor genes, that resists the natural and inherent death mechanism(s) embedded
3. DNA repair genes in cells (apoptosis and like processes), coupled with dysregulation of
cell proliferation events
Ideal Tumor Markers
• Only a few tumor markers have stood the test of time and entered in the diagnostic or
management algorithms for clinicians.
• Important characteristics of an ideal tumor marker are:

a) It should be highly specific to a given tumor type,
b) It should provide a lead-time over clinical diagnosis and
c) It should be highly sensitive to avoid false positive results.
d) The levels of the marker should correlate reliably with the tumor burden,
e) Accurately reflecting any tumor progression or regression, along with a short half-life allowing frequent
serial measurements.
f) Cheap and easy to perform
Sharma, S. 2009. Tumor Markers in Clinical Practice: General Principles and Guidelines. Indian
Journal of Medical and Paediatric Oncology, 30(1): 1-8.
Usage
• Although tumor markers are usually imperfect as screening tests for detection of occult
(hidden) cancers, once a particular tumor has been found using a marker, the marker may
be a way of monitoring the success (or failure) of treatment
• The tumor marker level may also reflect the extent (the stage) of the disease  indicating
how quickly the cancer is likely to progress and helping to determine the prognosis
(outlook)
Advantages and Diasadvantages
• Screening and early detection of cancer

• Aid in the diagnosis of cancer
• Determine response to therapy
• Prognostic indicator of disease progression
• Indicate relapse during follow-up period
• Being able to deduce diagnostic patterns that are unique to specific cancer states is a
challenge because of the biological variability in an individual patient's sample  low
specifity problem
• Differences in sample collection, handling or storage, and profiling techniques among

various research sites may change the protein profile obtained from a given sample
• A major problem in the identification of cancer biomarkers is the very low concentrations of
markers obtained
Other problems associated with the identification of cancer biomarkers are as follows
 Lack of reliability
 Proteins and/or modified proteins may vary among individuals, between cell types, and even within the
same cell under different stimuli or different disease states. Hence, it is difficult to know which value
obtained from an individual is accurate and what value in different patients indicates a problem
 Normal cells as well as cancer cells can produce most tumor markers
 Tumor markers are not always present in early-stage cancers
 Tumor markers can be present because of noncancerous conditions
 People with cancer may never have elevated tumor markers in their blood
 Even when tumor marker levels are high, they are not specific enough to confirm the presence of cancer.
Examples of
Tumor Markers
Carcinoembryionic Antigen (CEA)
Prostate Specific Antigen (PSA)
Human Chorionic Gonadotrophin (HCG)
CA-125
CA19-9
Proteins
Mitochondrial Markers
Carcinoembryonic Antigen (CEA)
• It is produced by embryonic tissue of gut, pancreas, and liver
• It is a complex glycoprotein elaborated by many different neoplasms
• Serum level is positive in:

1. 60–90% - Colorectal carcinoma
2. 50–80% - Pancreatic carcinoma
3. 25–50% - Gastric and breast carcinoma.
Carcinoembryonic Antigen (CEA)
• CEA is elevated in many benign disorders:

1. Alcoholic cirrhosis
2. Hepatitis
3. Ulcerative colitis
4. CEA assays lack both sensitivity and specificity required for detection of early cancers
Prostate-specific Antigen (PSA)
• Prostate specific antigen (PSA)  a 33 kDa serine protease belonging to the family of
“Kallikrein genes” and produced by both normal as well as neoplastic prostate epithelial
cells.
• PSA was first identified by in 1971 while attempting to find a substance in seminal fluid
that would aid in the investigation of forensic cases
• PSA is present in small quantities in the serum of normal men, and is often elevated in the
presence of prostate cancer and other prostate disorders.
• Prostate cancer can also be present in the complete absence of an elevated PSA level
Bhatt, A. N., Mathur, R., Farooque, A., Verma, A., & Dwarakanath, B. S. 2010. Cance Biomarkers: Current
Perspectives. Indian J Med Res, 132: 129-149.
Prostate-specific Antigen (PSA)
• Obesity has been reported to reduce serum PSA levels74, while increase has been found in
prostate infection, irritation, benign prostatic hyperplasia (BPH), and ejaculation
• A blood test to measure PSA is considered the most effective test currently available for
the early detection of prostate cancer.
• Human chorionic gonadotrophin (hCG) is a hormone produced normally by the placenta
• Its level is elevated in the blood of patients with certain types of testicular and ovarian
cancers (germ cell tumours) and choriocarcinoma
• Synthesis of free βhCG and its subunits by pelvic carcinomas such as those of the colon,
urinary tract, prostate, uterus and vulvo-vagina has also been reported
• The presence of increased serum levels of hCG and its metabolites  generally considered
to be a sign of a poor prognosis and it has been suggested that βhCG might directly
modify the growth of the cancer, leading to a worse outcome.
• The clinical use of free βhCG as a tumour marker has been limited to a small number of
patients owing to a short half life and rapid renal clearance
CA-125
• The CA 125 antigen is a membrane glycoprotein produced by tissues derived from

coelomic epithelium that is expressed by most epithelial ovarian cancers
• CA125 was initially detected in 1983 using the monoclonal antibody designated OC125
• CA125 is a powerful index of risk of ovarian and fallopian tube cancer in asymptomatic
postmenopausal women
• It is found in the serum of more than 80 per cent of the patients with epithelial ovarian
tumours, with half life of 4 days  Normal values of CA125 in serum range from 0 to 35
U/ ml
CA19-9
• CA19-9 (cancer antigen 19-9) or GICA(gastrointestinal cancer antigen) is a glycolipid with

unknown biological function
• The concentration of Ca 19-9 in serum has been shown to be a sensitive and specific
marker for pancreatic cancer, while its elevated levels in urine have been found in bladder
cancer
• Can be used to diagnose pancreatic carcinoma, hepatobiliary carcinoma (carcinoma of the

liver, carcinoma of the bile ducts) and carcinoma of the stomach
• The normal blood levels of CA 19-9 are below 37 U/ml

Proteins
Detection of four proteins in the saliva of cancer patients has been found to be the useful
markers of oral cancer with 90% sensitivity and 83% specificity for oral squamous cell
carcinoma, they are:
Calcium-binding protein MRP14 implicated in several types of cancer;
CD59 overexpressed on tumor cells that enables them to escape from complement-
dependent and antibody-mediated immune responses;
Profilin 1, a protein involved in several signaling pathways with cytoplasmic and nuclear
ligands, generally secreted into tumor microenvironments during the early progressive stage
of tumorigenesis;
Catalase, a member of the enzymatic antioxidative system, whose level is elevated in many
human tumors and involved in carcinogenesis and tumor progression
Mitochondrial Markers
• Several mutations in the mtDNA, particularly in the D-loop region, have been recently found
in breast, colon, esophageal, endometrial, head and neck, liver, kidney, leukemia, lung,
melanoma, oral, prostate, and thyroid cancers
• The majority of these somatic mutations are homoplasmic in nature, suggesting that the
mutant mtDNA played an active role in tumour formation
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Hendy Wijaya, MD, M. Biomed

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Tumor Markers

dr. Hendy Wijaya, M. Biomed

Hendy Wijaya, MD, M. Biomed 2

• Tumor markers are biochemical indicators of presence of a tumor  it refers to a molecule

• Cancer is a cluster of diseases involving:

• Alterations primarily in three main classes of genes, namely:

• Important characteristics of an ideal tumor marker are:

• Screening and early detection of cancer

• Differences in sample collection, handling or storage, and profiling techniques among

• It is produced by embryonic tissue of gut, pancreas, and liver

• It is a complex glycoprotein elaborated by many different neoplasms

• Serum level is positive in:

• CEA is elevated in many benign disorders:

• Human chorionic gonadotrophin (hCG) is a hormone produced normally by the placenta

• The CA 125 antigen is a membrane glycoprotein produced by tissues derived from

• CA19-9 (cancer antigen 19-9) or GICA(gastrointestinal cancer antigen) is a glycolipid with

• Can be used to diagnose pancreatic carcinoma, hepatobiliary carcinoma (carcinoma of the

• The normal blood levels of CA 19-9 are below 37 U/ml

Hendy Wijaya, MD, M. Biomed

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