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Tumor Markers
Outline
• Basic concepts and terminology
• Cancer
– Benign versus malignant
– Metastasis
– Staging
• Clinical utilities of tumor markers
• Examples of tumor markers and their uses
1
Basic concepts and terminology
• Two major processes involved in cell growth:
– Proliferation: the growth or production of cells by
multiplication
– Differentiation: cellular differentiation is the process by
which a less specialized cell becomes a more specialized
cell type.
• Cancer is a disease of abnormal growth.
• When the growth and development of normal cell loses
control, tumor cells begin to appear, which is called
tumorigenesis.
Definition of cancer
• According to the American Cancer Society, cancer is a group of diseases
characterized by uncontrolled growth and spread of abnormal cells
• It consists of more than 100 different diseases
• Cancer can arise in many sites and behave differently depending on its organ of
origin.
– Breast cancer, for example, has different characteristics than lung cancer.
Cancer originating in one body organ takes its characteristics with it even if it
spreads to another part of the body. For example, metastatic breast cancer in the
lungs continues to behave like breast cancer when viewed under a microscope,
and it continues to look like a cancer that originated in the breast.
• Cancer is an abnormal, continuous multiplying of cells. The cells divide
uncontrollably and may grow into adjacent tissue or spread to distant parts of the
body. The mass of cancer cells eventually become large enough to produce lumps,
masses, or tumors that can be detected.
Neoplasia and hyperplasia
• Neoplasia and hyperplasia are two similar biologic processes
• Hyperplasia involves the multiplication of cells in an organ or tissue, which
may consequently have increased in volume.
• Neoplasia involves the possibility of normal cells undergoing cancerous
proliferation as hyperplasia taking place under less controlled conditions; it
is, therefore, a form of pathologic hyperplasia.
• The major difference between them is how growth is controlled.
• Hyperplasia serves a useful purpose and is controlled by stimuli, whereas
neoplasia is unregulated and serves no purpose.
• The elevation of tumor marker in the case of the hyperplasia will be
transient, whereas neoplasia will be long lasting phenomena
Characteristics of Cancer
1. Abnormality
• Cells are the structural units of all living things.
• Trillions of cells are found in human,
• Cells carry out all kinds of functions of life: the beating of the heart,
breathing, digesting food, thinking, walking, and so on.
• However, all of these functions can only be carried out by normal
healthy cells.
• Some cells stop functioning or behaving as they should  serving no
useful purpose in the body at all, and become cancerous cells.
Characteristics of Cancer
2. Uncontrollability
• The most fundamental characteristic of cells is their ability to reproduce
themselves.
• They do this simply by dividing.
• The division of normal and healthy cells occurs in a regulated and
systematic fashion. In most parts of the body, the cells continually divide
and form new cells to supply the material for growth or to replace injured
cells. For example, when you cut your finger, certain cells divide rapidly
until the tissue is healed and the skin is repaired. They will then go back to
their normal rate of division.
• In contrast, cancer cells divide in a random manner. The result is that they
typically go into a non-structured mass or tumor.
Characteristics of Cancer
3. Invasiveness
• Tumors destroy the part of the body in which they originate and then spread
to other parts where they start new growth and cause more destruction 
invasive cancer.
• This characteristic distinguishes cancer from benign growths, which remain
in the part of the body in which they start.
• Although benign tumors may grow quite large and press on neighboring
structures, they do not spread to other parts of the body.
• Frequently, they are completely enclosed in a protective capsule of tissue
and they typically do not pose danger to human life like malignant tumors
Cancer and its consequences
• In western societies one death in five is caused by cancer
• The effects of tumor growth may be local or systemic
– E.g. obstruction of blood vessels, lymphatics or ducts,
damage to nerves, effusions, bleeding, infection, necrosis
of surrounding tissues and eventually death of the patient.
• The cancer cells may secrete toxins locally or into the general
circulation
– Both endocrine and non-endocrine tumors may secrete
hormones or other regulatory molecules
Local effects of tumors
• The local growth of a tumor can cause a wide range of abnormalities in
commonly requested biochemical tests
• This may be a consequence of obstruction of blood vessels or ducts
– e.g. the blockage of bile ducts by carcinoma of head of pancreas
causes elevated serum alkaline phosphatase and sometimes jaundice
• The liver is often the site of metastatic spread of a tumor
• Metastatic spread of a tumor to an important site may precipitate
complete system failure
– For example, destruction of the adrenal cortex by tumor causes
impaired aldosterone and cortisol secretion
Local effects of tumors
• Rapid tumor growth gives rise to abnormal biochemistry
– Leukemia and lymphoma are often associated with elevated
serum urate concentrations
– Serum lactate dehydrogenase is often elevated
– Large tumor may cause lactic acidosis
• Renal failure may occur in patients with malignancy for the
following reasons:
1.
2.
3.
4.
5.
obstruction of the urinary tract
hypercalcemia
Bence-Jones proteinuria
hyperuricemia
nephrotoxicity of cytotoxic drugs
Cancer cachexia
•
Cancer cachexia: bad condition describes the wasting characteristics that are usually seen
in cancer patients like weight loss, wasting of muscle, loss of appetite, and general debility
that can occur during a chronic disease
•
The features include anorexia, lethargy, weight loss, muscle weakness, anemia and pyrexia.
•
The development of cancer cachexia is due to many factors and is incompletely understood
1. inadequate food intake.
2. impaired digestion and absorption.
3. competition between the host and tumor for nutrients. The growing tumor has a high
metabolic rate and may deprive the body of nutrients. One consequence of this is a fall
in the plasma cholesterol level in cancer patients.
4. increased energy requirement of the cancer patients. The host reaction to the tumor is
similar to the metabolic response to injury, with increased metabolic rate and altered
tissue metabolism.
•
Certainly, there is an imbalance between dietary calories intake and body requirements
Cancer cachexia
• Tumor spread may cause infection, dysphagia
(difficulty in swallowing), persistent vomiting and
diarrhea
• The observation that small tumors can have profound
effect on host metabolism suggests that cancer cells
secrete or cause the release of humoral agents that
mediate the metabolic changes of cancer cachexia
• Some of these, such as tumor necrosis factor, have
been identified
Differences between normal and cancer cells
•
When either differentiation or proliferation becomes unregulated, there is a
risk for normal cells to be converted into cancer cells
•
This process is usually associated with changes of the genetic components of
the cell
•
Changes include:
1.
Mutation of cellular oncogenes (oncogene is a gene that, when mutated or
expressed at high levels, helps turn a normal cell into a tumor cell).
2.
Abnormal regulation of their expression.
3.
Rearrangements of oncogenic DNA sequences (oncogenic: describing a
substance, organism, or environment that is known to be a casual factor in
the production of a tumor). Some animal viruses are known to be oncogenic;
others are suspected of being so in man, including some papovaviruses,
adneviruses, and herpesviruses
Benign and malignant tumors
• Most tumor cells undergo a benign stage, gradually progress to malignancy,
and eventually become metastasized if not treated.
• The genetic instability associated with tumor cells can make tumor cells
more susceptible to additional mutations, which may ultimately lead to
malignant disease.
• During the benign stage, tumors remain at the primary site and present a
smaller risk to the host. At this stage, the patient stands a good chance of
being treated, such as by complete removal of tumor  the early detection of
a benign tumor is critical to cancer prevention in general and to high-risk
families in particular.
• All benign tumors are well differentiated and composed of cells resembling
the mature normal cells from the tissue of origin of the neoplasm.
Benign and malignant tumors
• Benign tumors:
– are not cancerous
– can usually be removed
– do not come back in most cases
– do not spread to other parts of the body, and the cells do not invade other
tissues
• Malignant tumors:
– are cancerous
– can invade and damage nearby tissues and organs
– metastasize (cancer cells break away from a malignant tumor and enter
the bloodstream or lymphatic system to form secondary tumors in other
parts of the body)
Metastasis
• Most cancer deaths are associated with metstatic disease.
• Metastasis is a multistep processes involving numerous tumor cell-host cell and
cell-matrix interactions.
• For tumor cells to metastasize:
– the tumor cells at the primary site have to first penetrate their adjacent
surroundings, including the epithelial basement membrane and the stroma.
– they then invade blood or lymphatic vessels and are carried to distant sites,
until they are finally arrested in the venous/capillary beds or solid tissue of a
distant organ.
– in this new environment, these tumor cells must again penetrate the vascular
walls to proliferate at the new distant site.
17
Metastasis
• In general, the larger, more aggressive, or more rapidly growing the primary
neoplasm, the greater the likelihood that the tumor cells will metastasize.
• Metastasis is highly selective process.
• Cells isolated from individual tumors may differ in many ways:
– with respect to capacity for invasion and metastasis.
– growth rate.
– cell surface receptors.
– immunogenicity
– response to cytotoxic drugs.
Signal transduction pathway
• The pathway of signal transduction controls both cell cycle and apoptosis
• The pathway is an orderly and specific transmission of growth-regulatory
messages from outside the cell to the machinery controlling replication
inside the cell nucleus.
• On binding of the stimulus to the receptor, the transmission of signal is
carried out by protein phosphorylation involving activation of the enzymatic
function of many kinases.
• These stimuli include hormones, insulin, cytokines, epidermal growth factor
and others
Cell cycle
• The cell cycle is one of the most
important determining factors controlling
cell proliferation.
• Cell cycle is tightly regulated and
controlled with different factors (Cyclin
A, Cyclin-dependent kinases: CDK2,
Cyclin D1 , CDK4 and others)
• Tumors results from the absence of
certain cell cycle controls.
• Defects in the cell cycle machinery may,
therefore, help cause cancer
Apoptosis
• The balance between cell proliferation and cell
death is affected by apoptosis.
• Apoptosis, a programmed cell or physiologic
death, is a natural self-destruct system present
in all cells.
• Failure of cells to undergo apoptotic cell death
may lead to cancer.
• It is a natural process the body employs for the
replacement of cells and the deletion of
damaged cells.
• Apoptosis is a control mechanism for tissue
remodeling during growth and development 
apoptosis provides a way for the body to
eliminate cells that have developed improperly,
or that have sustained genetic damage.
Angiogenesis
• Is a fundamental process by which new blood vessels are
formed
• Tumor growth and metastasis are angiogenesis-dependent
• A tumor must continuously stimulate the growth of new
capillary blood vessels for the tumor to grow
• Angiogenesis is critical, not only for growth of cancer
mass but also for the shedding of primary cells from the
primary tumor and development of metastases
General categories of cancers
• Carcinomas are cancers that occur in epithelial surfaces; the cells
that form the outer surface of the body to line or cover the body's
cavities, tubes and passageways.
• Adenocarcinomas are cancers that form on a glandular surface,
such as the lung, breast, prostate, ovary, or kidney
• Sarcomas are cancers that occur in supporting structures, such as
bone, muscle, cartilage, fat, or fibrous tissue
• Leukemias and lymphomas are cancers that occur in blood cell
elements
• Brain cancers, nerve cancers, melanomas, and certain testicular and
ovarian cancers do not fall into this general categories
Carcinoma
Adenocarcinoma
Osteosarcoma
Ectopic hormones
•
Some cancers secrete hormones, even though the tumor has not arisen from an endocrine
organ  Referred as ectopic hormone production,
•
Small cell carcinomas (Common malignant neoplasm of bronchus) are the most
aggressive of the lung cancers and are associated with ectopic hormone production 
Ectopic ACTH secretion: Adrenocorticotropic hormone secreted by the anterior pituitary
gland and stimulate androgens and cortisol release from the adrenal cortex  causing
Cushing’s syndrome
•
Patients with malignancy develop SIAD (syndrome of inappropriate antidiuretic
hormone). High levels of ADH  water is retained and patients present with
hyponatremia. This is probably the commonest biochemical abnormality seen in patients
with cancer and is almost invariably due to pituitary ADH secretion in response to nonosmotic stimuli
•
Some cancers may cause hypercalcemia. In many cases this is due to the secretion of
parathyroid hormone related protein (PTHrP), so-called because of its relationship with
PTH in its structure and function.
Grading
• Cancer can be described by tow ways grading and staging
• A biopsy is examined microscopically
– Low grade: slow growing, well differentiated, less aggressive, and less
likely to spread quickly
– Intermediate grade
– High grade: fast growing, poorly differentiated, tend to be more
'aggressive', and are more likely to spread quickly
• Grading systems differ depending on the type of cancer
– For example, breast cancers are graded 1, 2 or 3 which is much the same
as low, intermediate and high grade
– Another example is prostate cancer which is graded by a Gleason Score
Staging
• Staging: to determine the presence and site of metastases
from a primary tumor in order to plan therapy.
• In addition to clinical examination, a variety of imaging and
surgical techniques may be employed to provide a more
accurate assessment.
– Stage 0 or carcinoma in situ: Carcinoma in situ is very
early cancer. The abnormal cells are found only in the
first layer of cells of the primary site and do not invade
the deeper tissues.
Staging
– Stage I: Cancer involves the primary site, but has not
spread to close tissues. Stage IA and Stage IB.
– Stage II: Cancer has spread to nearby areas but is still
inside the primary site. Stage IIA and Stage IIB.
– Stage III : Cancer has spread throughout the nearby area.
– Stage IV: Cancer has spread to other parts of the body.
Stage IVA and Stage IVB.
Recurrent: Recurrent disease means that the cancer has come
back (recurred) after it has been treated.
Tumor markers
 Tumor markers are substances that can be detected in higher-than-normal amounts in the
blood, urine, or body tissues of some patients with certain types of cancer.
 Tumor markers are produced either by the body in response to the presence of cancer or
certain benign (non-cancerous) conditions or by the tumor itself. Their measurement or
identification is useful in patient diagnosis or clinical management.
 A tumor marker has been secreted or released by the tumor cells. Such markers are not
necessarily unique products of the malignant cells, but may simply be expressed by the
tumor in a greater amount than normal cells.
 The ideal marker would be
 a “blood test” for cancer.
 a positive result would occur only in patients with malignancy.
 one that would correlate with stage and response to treatment.
 that was easily and reproducibly measured.
No tumor marker now available has met this ideal.
Tumor Markers
Tumor markers are molecules occurring in blood
or tissue that are associated with cancer and
whose measurement or identification is useful in
patient diagnosis or clinical management.
Clinical utilities of tumor markers
Tumor markers can be used for one of the following purposes:
1. Screening a healthy population or a high risk population for the presence
of cancer even that most tumor markers, lack specificity and sensitivity.
2. Monitoring the course in a patient in remission or while receiving surgery,
radiation, or chemotherapy gives an indication of the effectiveness of
antitumor drug used.
3. Detection of recurrence following surgical removal of the tumor Because
patients being monitored have already had their cancer identified, the
specificity of the tumor marker is less important than sensitivity. The
sensitivity is important to detect recurrence as early as possible.
Clinical utilities of tumor markers
4. Determining the prognosis in a patient is usually based on tumor aggressiveness:
– a. determine how a patient should be treated
– b. indicate risk and predict the length of a relapse-free
– c. survival period at the time of primary therapy.
5. early detection and making an early diagnosis of cancer or of a specific type of
cancer allows the detection of early neoplasms at the curable stage.
No test meets all of those requirements
Tumor Antigens
Include markers defined by both monoclonal antibodies and polyclonal antisera, called
oncofetal antigens. The oncofetal substances, present in embryo or fetus, diminish
to low levels in the adult but reappear in the tumor.
Carcinoembryonic Antigen (CEA)
•
The CEA was one of the first oncofetal antigens to be described and exploited
clinically.
•
It is a complex glycoprotein that is associated with the plasma membrane of tumor
cells.
•
CEA is a normal cell product that is over-expressed by adenocarcinomas, primarily
of the colon, rectum, breast and lung.
•
CEA is the most widely used tumor marker for gastrointestenal cancer (colon)
•
Elevated CEA levels are found in a variety of cancers colon, pancreatic, gastric, lung,
and breast cancer.
•
It is normally found in small amounts in the blood of most healthy people but may
become elevated in people who have cancer or certain benign conditions.
Carcinoembryonic Antigen (CEA)
• Elevated CEA levels can also occur in patients with non-cancerous conditions,
including inflammatory bowel disease, pancreatitis and liver disease, chronic
lung disease, cirrhosis.
• The CEA was found to be elevated in up to 19 percent of smokers and in 3 percent
of a healthy control population.
• The test for CEA cannot substitute for a pathological diagnosis.
• As a screening test, the CEA is also inadequate.
• The CEA has been suggested as having prognostic value for patients with colon
cancer.
• CEA values have been positively correlated with stage and negatively correlated
with disease free survival.
• The CEA is of some use as a monitor in treatment. Usually the CEA returns to
normal within 1 to 2 months of surgery,
α1-Fetoprotein
• α -Fetoprotein is a normal fetal serum protein synthesized by the liver, yolk
sac, and gastrointestinal tract
• It is a major component of fetal plasma, reaching a peak concentration of 3
mg/ml at 12 weeks of gestation. Following birth, it clears rapidly from the
circulation, having a half life of 3.5 days, and its concentration in adult
serum is less than 20 ng/ml.
• AFP is of importance in diagnosing hepatocellular carcinoma and may be
useful in screening procedures.
• An elevated AFP has been termed “the single most discriminating laboratory
test indicative of malignant disease now available”  it could be valuable
in screening for hepatocellular carcinoma in high risk populations.
α1-Fetoprotein
• The AFP is less frequently elevated in other malignancies such as pancreatic
cancers, gastric cancers, colonic cancers, and bronchogenic cancers. This
elevation was not necessarily associated with liver metastases
• The AFP is rarely elevated in healthy persons, and a rise is seen in only a
few disease states like liver diseases, viral or drug induced hepatitis.
• Thus, AFP is a useful marker in hepatocellular carcinoma and germ cell
tumors
• The AFP is high in the first trimester of gestation and in the case of the
presence of neural tube defect
• Newborn have much higher serum AFP than adults
CA 125
• CA125 is an antigen present on most of ovarian carcinomas.
• It is defined by a monoclonal antibody (OC125) that was generated by immunizing
laboratory mice with a cell line established from human ovarian carcinoma.
• It circulates in the serum of patients with ovarian carcinoma and investigated for
possible use as a marker.
• The level CA125 correlates with patient response to treatment of ovarian cancer
• The CA125 is elevated in other cancers including uterus, cervix, pancreatic, lung,
breast, and colon cancer, and in menstruation, pregnancy, and other gynecologic and
non gynecologic conditions.
• Changes in CA 125 levels can be used effectively in the management of treatment
for ovarian cancer.
• CA 125 levels can also be used to monitor patients for recurrence of ovarian cancer.
CA19-9
• CA19-9 is defined by monoclonal antibody generated against a colon
carcinoma cell line to detect a mono sialo-ganglioside found in patients
with gastrointestinal adenocarcinoma.
• It is found it to be elevated in 21 to 42 percent of cases of gastric cancer, 20
to 40 percent of colon cancer, and 71 to 93 percent of pancreatic cancer,
and has been proposed to differentiate benign from malignant pancreatic
disease
• CA 19-9 has also been identified in patients with hepatocellular cancer and
bile-duct cancer.
• Non-cancerous conditions that may elevate CA 19-9 levels include
gallstones, pancreatitis, cirrhosis of the liver, and cholecystitis.
• CA 19-9 can be used in monitoring of the patients and recurrent cancer
Prostate-Specific Antigen (PSA)
•
PSA is tissue specific tumor marker; it is found in normal prostatic epithelium and secretions
but not in other tissues.
•
It is a glycoprotein, whose function may be to lyse the seminal clot.
•
PSA is highly sensitive for the presence of prostatic cancer. The elevation correlated with
stage and tumor volume.
•
It is predictive of recurrence and response to treatment.
•
PSA is the first tumor marker recommended for screening of prostate cancer in men older
than age 50
•
It found in two major forms: free form and PSA-α-antichymotrypsin (PSA-ACT) complex.
•
Measuring the ratio between the free and complexes of PSA helps to differentiate benign prostate
hyperplasia from prostate cancer
Age Range (Years)
Caucasians
[ng/ml]
40 - 49
0.0 - 2.5
50 - 59
0.0 - 3.5
60 - 69
0.0 - 4.5
70 - 79
0.0 - 6.5
Hormones
• Hormones are produced by many tumors. The hormone may be:
– a natural product of affected cells by cancer:
• Insulin production by islet cell tumor,
• Calcitonin by medullary thyroid carcinoma,
• Catecholamines by pheochromocytoma.
– The hormone is not a natural product of its associated organ, in
which case is designated “ectopic”. Examples include the
production of ACTH and ADH by lung cancers.
Calcitonin
• Calcitonin is a hormone produced by parafollicular C cells in the thyroid gland.
• It helps to regulate blood-calcium levels.
• In cancers of the parafollicular C cells, called medullary carcinomas of the thyroid,
levels of this hormone are elevated.
• Calcitonin is one of the rare tumor markers that can be used to help diagnose early
cancer.
• Because medullary carcinoma of the thyroid is often inherited, blood calcitonin can
be measured to detect the cancer in its earliest stages in family members who are at
risk.
• Other cancers, particularly lung cancers, can produce calcitonin, but measurement of
its level in the blood is not usually used to follow these cancers.
Human Chorionic Gonadotropin (hCG)
• HCG is a glycoprotein consisting of subunits α and β, which are
nonconvalently linked.
• The hormone is normally produced by the trophoblastic cells of the
placenta and is elevated in pregnancy.
• hCG is elevated in the urine and serum during the pregnancy
• Its most important uses as a tumor marker are in gestational
trophoblastic disease (a group of rare pregnancy-related tumours)
and germ cell tumors of ovary and testis.
• Gestational trophoblastic disease is proliferation of trophoblastic tissue in
pregnant causing excessive uterine enlargement, vomiting, vaginal
bleeding, diagnosis includes measurement of the β hCG.
Human Chorionic Gonadotropin (hCG)
• All gestational trophoblastic tumors produce HCG, and it is a valuable
marker in these tumors,
•
HCG is extremely sensitive, being elevated in women with minute
amounts of tumor.
• Free β- HCG is occasionally elevated in ovarian cancer and lung
cancers breast, lung, and gastrointestinal tract, but in these diseases it
has found little clinical application.
• Free β- HCG is sensitive and specific for aggressive neoplasmas
Thyroglobulin
• Produced by the thyroid gland
• Thyroglobulin is elevated in many thyroid diseases
• When a thyroid cancer is surgically removed, the whole thyroid
gland is usually also removed
• Therefore, any elevation of the thyroglobulin level above
10ng/ml suggests that the cancer has returned
• Metastatic thyroid cancer
• It is used to evaluate the effectiveness of treatment for thyroid
cancer and to monitor for recurrence
Enzymes
Enzymes that can be used as markers are either native to normal tissue or
associated with changes in metabolism that are unique to cancer tissue.
Neuron Specific Enolase
• Neuron specific enolase is an isozyme of the glycolytic pathway that is found
only in brain and neuroendocrine tissue.
• It is an immunohistochemical marker for tumors of the central nervous system,
neuroblastomas.
• NSE has been detected in patients with neuroblastoma, small-cell lung cancer,
Wilms' tumor (a malignant tumor of the kidney is called also nephroblastoma),
melanoma, and cancers of the thyroid, testicle and pancreas.
•
NSE as a tumor marker has concentrated primarily on patients with
neuroblastoma and small-cell lung cancer.
Galactosyl Transferase II
• Galactosyl Transferase II, an isozyme of galactosyl transferase, has been
shown to be elevated in a variety of malignancies, predominantly
gastrointestinal.
• In colon cancer its level correlated with the extent of disease and disease
progression;
•
In pancreatic cancer it was more sensitive and specific in distinguishing
benign from malignant disease than CEA and other tests
Prostatic acid phosphatase
• It is capable of monitoring prostate malignancy
• It is rarely used now, because the PSA test is much more sensitive
Alkaline phosphatase (ALP)
• ALP has been used to detect mainly malignancies in bone and liver and to detect
metastases to these organs.
• Osteoblastic lesions in the bone produced by prostate cancer metastases give rise to
enormous elevations in ALP,
• Whereas lesions produced by metastatic breast cancer cause only mild or no
elevation.
• Other causes of elevated ALP include extrahepatic obstruction of the bilialy tract,
which usually results in a twofold increase in ALP levels.
• Diseases such as leukemia that infiltrate the liver can cause marked elevations in
ALP levels
• The source of the elevated ALP (bone or liver) can be identified by measuring other
liver enzymes, such as gamma-glutamyl-transferase and or by measuring ALP
activity
Creatine kinase (CK)
• Creatine kinase (CK) levels are helpful in establishing a diagnosis of myocardial
infarction.
• CK-BB (CKl) is found in the brain, gastrointestinal tract, uterus, and prostate.
Elevations of CK-BB (and total CK) can be found in prostatic carcinoma and
metastatic cancer of the stomach.
Immunoglobulins
• Production of a monoclonal immunoglobulin molecule is characteristic of multiple
myeloma.
• Bence Jones protein (paraproteins) are usually complete antibody molecules but may
be isolated light chains or, rarely, heavy chains.
• They may be lambda or kappa light chains and of any immunoglobulin subtype.
• Bence Jones protein found in high concentration in serum and in urine
• Immunoglobulins are valuable in the staging and treatment of myeloma, the amount
of paraprotein serving as an index of tumor volume.
Estrogen and progesterone receptors
• These intracellular receptors are measured directly in tumor tissue.
•
Most oncologists have used the estrogen and progesterone receptors not
only to predict the probability of response to hormonal therapy at the time
of metastatic disease, but also to predict the likelihood of recurrent
disease.
• These receptors are also used to predict the need for adjuvant hormonal
therapy or chemotherapy.
• The measurement of estrogen and progesterone receptors in biopsy
material has been used to determine which breast cancer patients will
respond to endocrine therapy, e.g. with the antiestrogen tamoxifen
Immunocytochemical identification of estrogen receptors in 8
μm frozen sections of human breast cancers using monoclonal
antibody. Cancers show low (left), moderate (center), or high
(right) proportions of receptor-containing cells. × 100.
Susceptibility genes
• Several familial cancers are associated with germ line mutations in various
genes
• The most prominent of these are the genes for susceptibility to breast and
ovarian cancer, such as BRCA1 and BRCA2
• BRCA1 & BRCA2 (breast cancer 1 & 2):
– Are human genes belong to a class of genes known as tumor suppressors,
– some mutations of which are associated with a significant increase in the risk of
breast cancer, as well as other cancers.
• Screening tests for BRCA1 and BRCA2 are now available to screen these
families for the identification of carriers
Limitations of tumor markers
• Tumor-marker levels can be elevated in people with
benign conditions
• Tumor-marker levels are not elevated in every person
with cancer, especially in the early stages of the
disease
• Many tumor markers are not specific to a particular
type of cancer.
• The level of a tumor marker can be elevated by more
than one type of cancer
Marker
Tumor
AFP
Germ cell
AFP
Hepatoma
HCG
Germ cell
HCG
Choriocarcino
ma
Ovarian
Screeni
ng

Diagno
sis
Progno
sis
Monitorin
g
Follo
w-up


















Prostate



PSA
Prostate



CEA
Colorectal


Calcitonin
Medullary
carcinoma of
thyroid
Endocrine








56
CA 125
Acid
phosphatase
Hormone
s
Paraprote
ins
Myeloma


Tumor markers that are used in University hospital:
1. Liver carcinoma: -fetoprotein
2. Ovarian carcinoma: CA 125
3. Colorectal cancer: CA 19.9
4. Pancreatic carcinoma: amylase, CEA (in case of liver
metastasis)
5. Breast cancer: BRACA1, BRAC2
6. Prostate cancer: PSA (total and free). Most PSA in the blood is
bound to serum proteins. A small amount is not protein bound and
is called free PSA. In men with prostate cancer the ratio of free
(unbound) PSA to total PSA is decreased. The risk of cancer
increases if the free to total ratio is less than 25%.
7. Non specific marker: hCG
The End