Download Tumor Markers

Tumor Markers
Lecture one
By
Dr. Reem Sallam
Objectives
 To briefly introduce cancers, their
incidence, some common terms, and
staging system.
 To be familiar with the definition of
tumor markers, and characteristics of
an ideal tumor marker.
 To know various applications of tumor
marker detection
Lecture outlines
 Overview
 Types of tumor markers
 Applications of tumor marker
detection:
 Screening
 Prognosis
 Monitoring effectiveness of therapy and
disease recurrence
Overview
 Cancer is the second leading cause of death
in North America, accounting for > 500,000
deaths annually.
 It is estimated that 45% of males and 38%
of females will develop invasive cancer in
their lifetime.
 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%
9%
Colorectal 11%
10%
Colorectal 10%
Common Cancer Terms
Angiogenesis
Development of new blood vessels to supply oxygen and
nutrients to cells
Apoptosis
Programmed cell death
Cell cycle
Phases of cell activity divided into G, S, and M (growth,
DNA synthesis, and mitosis, respectively)
Oncogene
Encodes a protein that, when mutated, promotes
uncontrolled cell growth
Tumor
suppressor gene
Encodes a protein involved in protecting cells from
unregulated growth
Overview,
continued…
 Biologically, cancer refers to the uncontrolled growth
of cells that can develop into a solid mass or tumor &
spread to other areas of the body.
 The formation (tumorigenesis) & spreading
(metastasis) of tumors are caused by a complex
combination of inherited and acquired genetic
mutations
 During tumorigenesis, these mutations include
activation of growth factors e.g. Epidermal Growth
Factor (EGF) & oncogenes (e.g. K-ras), in
combination with inhibition of apoptosis, tumor
suppressor, and cell cycle regulation genes.
Overview,
continued…

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
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.
1- Screening
 With the possible exception of Prostate-Specific
Antigen (PSA), no tumor marker identified to
date can be used to adequately screen
asymptomatic populations because most of the
clinically used tumor markers are found in normal
cells and benign conditions in addition to cancer cells.
 Screening asymptomatic populations would therefore
result in detection of false-positives-(patients without
disease with detectable tumor marker), leading to
undue alarm and cost to patients.
 Presently, only a few tumor markers are used in
populations with high incidence or other carefully
defined populations.
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%
2- Prognosis
 Tumor marker concentration generally increases with
tumor progression, reaching their highest levels when
tumors metastasize.
 Therefore, serum tumor marker levels at diagnosis can
reflect the aggressiveness of a tumor and help predict
the outcome for patients.
 High serum tumor markers at diagnosis might indicate
the presence of malignancy and possible metastasis
associated with a poorer prognosis.
 In other instances, the mere presence or absence of a
particular marker may be valuable. Such is the case with
some of the receptors used to base chemotherapeutic
treatment in breast cancer:

The presence of hormonal (estrogen & progesterone)
receptors in breast cancer  the cancer will respond to
hormonal therapy
3- Monitoring Effectiveness of
Therapy and Disease Recurrence
 One of the most useful applications of tumor markers
is monitoring therapy efficacy and detecting disease
recurrence.
 After surgical resection, radiation, or drug therapy of
cancer (chemotherapy), tumor markers are routinely
followed serially.
 In patients with elevated tumor markers at diagnosis,
effective therapy results in a dramatic decrease or
disappearance of the tumor marker.
 If the initial treatment is effective, the appearance of
circulating tumor markers can then be used as a
highly sensitive marker of recurrence.
Summary


Cancer is:

a broad term used to describe so many diseases

the second leading cause of death

the uncontrolled growth of cells that can develop into a solid mass or tumor &
spread to other areas of the body, where stage IV in accompanied by
metastasis

Caused by a complex combination of inherited and acquired genetic mutations
including activation of growth factors & oncogenes, and inhibition of apoptosis,
tumor suppressor, and cell cycle regulation genes.

is classified by a combination of several factors including: tumor size, histology,
regional lymph node involvement & the presence of metastasis into 4 stages

Sometimes detected and monitored using biologic tumor markers.
Tumor markers:

are produced either by the tumor or as an effect of the tumor on the host

encompass diverse molecules such as serum proteins, oncofetal antigens,
hormones, metabolites, receptors, and enzymes

Ideally, a tumor marker would be: tumor specific, absent in healthy individuals,
& readily detectable in body fluids.

Unfortunately, do not fit this ideal model.

No tumor marker can be used for diagnosis of tumors,

a host of them have been identified that have a high enough specificity &
sensitivity to be used in: screening asymptomatic populations at risk,
prognosis, detection of recurrence & monitoring response to treatment.
THANK YOU 