TUMOR MARKERS

Proliferation
Differentiation
Formation of solid mass or tumor
Activation of growth factors (e.g.,
epidermal growth factor [EGF])
Activation of oncogenes (e.g.,K-ras),
Inhibition of apoptosis, tumor
suppressor, and cell cycle regulation
genes (e.g., BRCA1, p53, cyclins)
Involves the multiplication of cells in an
organ or tissue, which may
consequently have increased in
volume.

Serves a useful purpose and is

controlled by stimuli

Elevation of tumor markers istransient.

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 successfully treated by the
complete removal of the tumor.

Early detection is critical to cancer

prevention in general to high risk families
in particular
Well differentiated and composed of cells
resembling the nature of normal cells from
the tissue of origin of the neoplasm.
Involves the possibility of normalcells
undergoing cancerous proliferation
Pathologic hyperplasia
Unregulated and serves no purpose
Elevation of tumor markers will be a long
lasting phenomenon if not treated
o Due to genetic instability of tumor cells.
refers to the uncontrolled growth of cells that
can develop into a solid mass or tumor and
spread to other areas of the body
Cause of the mostcancer deaths
Due to multiple genetic changes that result to
uncontrolled proliferation
Multistep processes involving numerous tumorcell-
host cell and cell-matrixinteractions.
Tumor cells at the primary site à penetrate their
adjacent surroundings (epithelial basement
membrane and the interstitialstroma.)
àinvade blood or lymphatic vessels to distant sites
à venous/capillary beds or solid tissue of a distant
organ.
It is a highly selectiveprocess.
Metastasis
Loss of cell adhesion proteins(e.g., β-catenin
and E-cadherin)
Activation of angiogenesis genes (e.g.,VEGF)
Tumor size
Histology
Regional lymph
Node involvement
Presence of metastasis
Four Stages – Roman Numerals I-IV
Disease severity
higher stages are indicative of significantspreading
and severe systemic disease
Disease Progression
proliferation and metastasis occur at theexpense
of normal organ processes à cause of morbidity
and mortality
Tumor Markers
Produced either directly by the tumor or as
an effect of the tumor on healthy tissue
(host)

Used to:
Differentiate a tumor from normal tissue
Detect the presence of a tumor based on
measurements in the blood or secretions
CLINICAL UTILITIES
OF TUMOR
MARKERS
None of the tumor markers discovered had
sufficient specificity and sensitivity forscreening
in the general population
It is not recommended for most tumor markers,
especially in an asymptomaticpopulation
The screening of primary hepatoma in Asian
countries is based on the measurement of
serum AFP.
First tumor marker recommended for screening for prostate
cancer in men older than age of 50.
The purpose was to detect prostate cancer at early curable
stages, when the tumor is still confined inside the organ.
Two major forms: Free PSA and a PSA –alpha1-
antichymotrypsin (PSA-ACT)
Free PSA percentage of free PSA to PSA-ACT ratio may help
differentiate benign prostate hyperplasia (BPH) from prostate
cancer.
Several familial cancers are associatedwith
germline mutations in variousgenes.
The most prominent are genes for susceptibility
to breast and ovarian cancer, such as BRCA1 and
BRCA2 are now available to screen these
families for the identification ofcarriers.
One of the two most useful
applications of tumor markers
involves their use in monitoring
the course during treatment of
the cancer patient.
Monitoring tumor markers for the
detection of the recurrence following
the surgical removal of the tumor.

It is desirable to monitor the patient

using a highly sensitive tumor
marker test to detect recurrence as
early as possible.
Determination is based on the assessment of tumor
aggressiveness, which, in turn, determines how a
patient should be treated.

Prognostic factors measured inthe clinical laboratory

also indicate risk and predict the length of a relapse-
free, as well as overall, survival period at the time of
the primary therapy.

High levels of serum tumor marker measured during

diagnosis would indicate the presence of a malignant
or metastatic tumor associated with a poor prognosis.
Detecting the phenotypes in the blood
circulation corresponding to early
mutations of a cancer allows the
detection of early neoplasm at the
curable stage.

Measurement of all mutant phenotypes

and risk factors in the circulation would
help to identify individuals at risk for
cancer or detect early tumors in benign
state.
Previously, drugs used in chemotherapy were predominantly
DNA-active drugs that were considerably toxic and had limited
efficacy.
Inhibition of tumor cell proliferation may also be effective by
introducing agents (or genes) that turn off the signaling pathway
or pathways that specifically drive proliferation within a given
tumor or tumortype.
The prevailing new rationale is aimed at the development of
target-selective “smart” drugs on the basis of characterized
mechanisms of action.
The specific defect of the tumor identified by these new tumor
markers should, therefore, lead to the design of more specific
drugs, including antibodies and small molecules, which inhibit
growth factor receptors tyrosinekinases.
(1) oncofetal antigens, such as AFP and CEA,
which are normally expressed during fetal
development but do not occur normally in the
tissues or sera of children and adults
(2) proteins occurring in epithelial cells that
become elevated in tissue and serum in adeno-
and squamous cell carcinomas, such as the CA
19-9, CA 125, and CA 15-3 proteins
(3)polypeptide hormones, such as the β chain
of human chorionic gonadotropin (β-hCG), and
(4) specific enzymes, such as the placental
isoform of alkaline phosphatase, that become
elevated in the serum of patients with specific
tumors
a. α- Fetoprotein
- AFP is a major fetal serum protein and is also one
of the major carcinoembryonicproteins
- Elevated in patients with primary hepatoma
carcinoma cell (HCC) and yolk-sac-derived germ
cell tumors.
- Most useful serum marker for diagnosis and
management of HCC
b. b2 – Microglobulin (b2M)
-It is nonspecific tumor marker because
it is elevated, not only in solid tumors
but also in lymphoproliferative diseases
and variety of inflammatory disorders
including: RA, SLE, Sjogren’s syndrome,
and Crohn’s disease.

-Normal serum level – 0.9-2.5 mg/L

c. Cancer Antigen 125 (CA125)
- Defined first by a murine monoclonal antibody
OC 125 raised against a serous ovarian
carcinoma cell line.
- Useful for detecting ovarian tumors at an early
stage and for monitoring treatments without
surgical restaging.
- Upper normal limit – 35 U/mL.
d. Cancer Antigen 15-3 (CA 15-3) and CA 27.29
- >25 U/mL are observed in patients with metastatic
breast cancer
- More sensitive and specific marker for monitoring the
clinical course of patients with metastatic breast
cancer and is more sensitive marker for metastatic
breast cancer than CEA.
e. Cancer Antigen 19-9 (CA19-9)
- The highest sensitivity of CA 19-9 was found
in pancreatic and gastric cancers
- CA 19-9 is also related to Lewis blood group
substances. Only serum antigen from cancer
patients belonging to the Le (α-β+) or Le (α+β-)
blood group will be CA 19-9-positive
- CA 19-5 and CA50 have also been defined
by monoclonal antibodies that are only
slightly different from CA 19-9
useful marker for the management of
patients with gastric and colorectal
carcinoma

proposed as a specific marker for tumor

occurrence of resectable gastric cancer and a
prognostic marker for survival reported to be
an independent prognostic marker for survival
in colorectal in multivariate analysis together
with β-hCG and
CEA
Mostwidely used tumor marker for gastrointestinal
cancer today.
transforming growth factor (TGF)-α, fibroblastgrowth
factor, and Ras oncoprotein are all increased in
colorectal cancer and decreased after surgical
resection
mutations of DNA mismatch repair genes (e.g. hMSH2,
hMLH1 and hMSH6) are shown to be associated with
hereditary nonpolyposis colorectalcancer
one of the circulating peptide hormones that
may become elevated in patients withincreased
bone turnover rate associated with skeletal
metastases
ectopically elevated in bronchogenic carcinomas
and is also elevated in medullary carcinoma of
the thyroid.
(CYFRA 21-1)
elevated serum CYFRA 21-1 have concentrated on
breast cancer and squamous cell carcinoma of the lung
reflect the tumor mass in multiple studies with
correlation to tumor stage, survival, predictive rolein
surgical treatment for early stage disease and
chemotherapy for advanced stage non-small celllung
cancer
free β-subunit is useful for the detection of
recurrence or metastasis forchoriocarcinoma
when the intact hCG may remainnormal
Seminomatous testicular cancer contains both
intact hCG and β-hCG or free α subunits in equal
amounts
elevated in the sera of patients with a number
of different epithelial cell cancers, including
breast, lung, colorectal, and ovariancancers
It is a useful marker of exocytotic sympathoadrenal
activity in patients withpheochromocytoma.
medullary carcinoma of thyroid, and small-cell lung
carcinoma
increased serum chromogranin A levels are detected in
epithelial cancers with neuroendocrine differentiation,
including prostate, breast, ovary, pancreas, and colon
Above normal in tumors originating from neural
crest.
Useful in detection and monitoring of patients
with pheochromocytoma and diagnosis of
neuroblastoma in children
Found elevated in various malignantdiseases,
such as, in the breast, GI or lungs.
It is also altered in leukemia, lymphoma,
Hodgkin’s disease, and melamona, as well as in
nonmalignant infalammatory diseases.
a. Neuron-Specific Enolase (NSE)
- can be found in tumors originating from the
neuroendocrine cell system, including
glucagonomas and insulinomas.
b. Progesterone receptor (pgR)
- Associated with breast tumors
c. Prostate-Specific Antigen (PSA)
- Major protein in seminalplasma
Useful in monitoring squamous cell carcinomas
of the head and neck, lung, esophagus, and anal
canal.
Useful in detection and monitoring of patients
with pheochromocytoma and diagnosis of
neuroblastoma in children
T H A N K Y O U!!!