TUMOR MARKER Flashcards
Tumor markers refer to Mixture of different _____
analytes
Multiplication of cells, reproduce from mother cell to
daughter cells
proliferation
Maturity or maturation of cell
differentiation
is a term refers to Formation of solid mass or tumor
TUMORIGENESIS
processes which may cause in the formation of 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
HYPERPLASIA
Serves a useful purpose and is controlled by stimuli
HYPERPLASIA
in hyperplasia,
Elevation of tumor markers is __
transient
a type of Tumors that remain at the primary site and present a smaller
risk to the host
BENIGN
Site of overproduction, stay in long period of time, and
does not have capability to metastasized, present
smaller risk (cause obstruction)
benign
means to spread from one part of
the body to another
Metastasized
Well differentiated and composed of cells resembling the
nature of normal cells from the tissue of origin of the
neoplasm.
benign
__ in benign tumor is critical to cancer prevention in general to
high risk families in particular
o Prevent to progress to malignant
Early detection
a benign tumor
At this stage the patient stands a good chance of being
successfully treated by the
complete removal of the tumor
Neo means
new
called as Pathologic hyperplasia
neoplasia
Unregulated and serves no purpose
neoplasia
Elevation of tumor markers will be a long lasting
phenomenon if not treated
NEOPLASIA
involves the possibility of normal cells undergoing
cancerous proliferation (cancer cells
neoplasia
neoplasia can result into what type of tumor
cancerous - MALIGNANT
Due to genetic instability of tumor cell
malignant
malignancy that begins in the skin or in
tissues that line or cover internal organs
carcinoma
malignancy that begins in bone, cartilage, fat,
muscle, blood vessels, or other connective or supportive
tissue
sarcoma
malignancy that begins in blood-forming
tissue, such as the bone marrow → causes too many
abnormal blood cells to be made
leukemia
malignancies that
begin in the cells of the immune system
Lymphoma and multiple myeloma
Refers to the uncontrolled growth of cells that can develop
into a solid mass or tumor and spread (metastasized) to
other areas of the body
CANCER or MALIGNANCY
Capability of cancer cell to go from one organ to another
METASTASIS
Cause of the most cancer death
metastasis
Due to multiple genetic changes that result to uncontrolled
proliferation
metastasis
Metastasis
Multistep processes involving ____ interactions
numerous tumor cell- host
cell and cell-matrix interactions.
It is a mechanism in the body which affects metabolic
processes and controls the cell cycle and apoptosis
SIGNAL TRANSDUCTION PATHWAY
Orderly and specific transmission of growth-regulatory
messages from outside the cell to the machinery controlling
replication inside the cell nucleus.
SIGNAL TRANSDUCTION PATHWAY
this is how the cell communicates from the outside machinery eventually controlling the inside of the nucleus
SIGNAL TRANSDUCTION PATHWAY
Starting mechanism of transformation of cell from a normal
cell to a new or abnormal cell (neoplasia)
SIGNAL TRANSDUCTION PATHWAY
It involves the passage of a cell through a complete round of replication.
cell cycle
It is one of the most important determining factors controlling cell proliferation
CELL CYCLE
In most mammalian cells, the cell cycle is composed of four
phases:
G1
S
G2
M
G0
defined as the interval between the conclusion of
mitosis and start of DNA replication
G1
interval during which the nuclear genome is
replicated
S
a disruption in one of the phase of cell cycle will lead to
transformation of the cell
is result from the absence of certain cell cycle
controls
tumor
Defects in the cell cycle machinery may help cause cancer
true or false
true
Starting point in making abnormal cells
– fifth phase – metabolic compartment of reversibly
quiescent cells occupies
G0
A programmed cell or physiologic cell death
apoptosis
It is a natural self-destruct system present in all cells
apoptosis
Failure of cells to undergo apoptotic cell death may lead to
.
cancer
If there is inhibition of apoptosis it will cause a
cancer or
tumor production
It is the natural process the body, the replacement of cells
and the deletion of damaged cells inherent to normal
functioning of multicellular microorganism
apoptosis
Making sure that the cell proliferate and differentiated is
normal and functioning
apoptosis
It is a control mechanism for tissue remodeling during
growth and development in which it maintains what type of
cell develop in particular organ
apoptosis
It is also means of eliminating, removing an excess or
different type of cell which already undergo to mutation
or any genetic damage
apoptosis
Markers for apoptosis
p53 protein, Bcl 2, and Fas/Fas ligand
Markers of apoptosis
p53 protein, Bcl 2, and Fas/Fas ligand
they can be both ___ and __ of cell death
inducer or inhibitor
Markers: p53 protein, Bcl 2, and Fas/Fas ligand
These markers would have tremendous potential for
early diagnosis, prognosis, and therapeutic application
true or false
true
It refers to creating or making own vascular network
angiogenesis
New blood vessels are formed.
angiogenesis
Tumor growth and metastasis are ___ dependent .
angiogenesis-dependent
Cancer cells are very much effective in making sure
they spread through the body by creating own __
vascular network
It is critical, not only for the growth of solid tumors, but also for the shedding of cells from the primary tumor and the
development of metastases at distant sites.
true or false
true
purpose of new formed vessel network during angiogenesis
The new blood vessels embedded in a tumor provide a
gateway for tumor cells to enter the circulation and to
metastasize to distant sites
The degree of angiogenesis in an initial primary tumor
correlates with __ and ___ in
patients
metastatic spread and survival rates
Most well known angiogenic factors:
o Vascular endothelial growth factor (VEGF)
o Acidic and basic fibroblast growth factor (aFGF and bFGF)
o Transforming growth factor alpha (TGF-alpha)
If we prevent angiogenesis, we can prevent ___
metastasis
These are specific class of transmembrane glycoprotein
involved whenever cells are moving and interacting.
adhesion
__ allows cancer cell to incorporate within
basement membrane in an organ
Adhesions
They regulate the migration of leukocytes to sites of
inflammation or into lymphatic tissue.
adhesion
the organ that is Once invaded it is once step away on
moving from one organ to another
lymph node
Three classes of adhesions (adhesive proteins)
o Selectins
o Integrins
o Immunoglobulin family
cancer progression
activation of oncogenes
upregulation of proteases
deactivation of adhesion molecules
stimulation of angiogenesis genes
mutation of cell cycle and dna repair genes
loss of tumor suppressor genes
growth factor dysregulation
FACTORS CONSIDERED IN CANCER SEVERITY
- Tumor size
- Extent of invasion
- Histology (histologic assessments (basis for the TNM staging system))
- Regional lymph
- Lymph node involvement
- Presence of metastasis
Primary responsibility of a medical technology is to prepare
the slide obtained through biopsy
true or false
true
are responsible for
determining how severe the condition through analyzing the prepared slides
Pathologist and medical practitioner
CANCER STAGING are indicated as
I-IV
higher stages are indicative of significant spreading and
severe systemic disease
Disease severity
proliferation and metastasis occur at the expense of normal organ processes → cause of morbidity and mortality
Disease Progression
cancer stage
Localized primary tumor
* tumor cells are within the bassement
membrane
stage 1
cancer stage
Invasion of primary tumor through epithelium and into blood vessels
* undergo angiogenes
stage 2
cancer stage
Migration of tumor into regional lymph nodes
stage III
cancer stage
Metastasis and invasion of tumor to distant tissues
(adjacent tissue)
stage IV
Produced either directly by the tumor or as an effect of the
tumor on healthy tissue (host)
tumor marker
TUMOR MARKERS are used to
o Differentiate a tumor from normal tissue
o Detect the presence of a tumor based on measurements in the blood or secretions
Increased enzymes are always indicating or directly related to carcinoma
true or false
false
Tumor markers are a stand alone procedures.
t or f
false
FUNCTIONAL CLASSIFICATION OF TUMOR MARKERS
oncofetal antigens
proteins
polypeptide hormones
specific enzymes
oncofetal antigens examples
alpha-feto protein
Carcinoembryonic antigen
a classification of tumor marker 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
oncofetal antigens
a classification of tumor marker that is occurring in epithelial cells that become
elevated in tissue and serum in adeno and squamous cell
carcinomas
proteins
example of proteins tumor marker
CA 19-9, CA 125, and CA 15-3 proteins
this classification of tumor marker that includes, serum and protein, light chain, macroglobulin,
cancer antigen markers
protein marker
polypeptide hormones tumor marker example
B chain of chorionic gonadotropin
serum test used as a tumor marker for testicular carcinoma
B chain of human chorionic gonadotropin (B-hCG)
example of specific enzyme that is a tumor marker
placental isoform
it become elevated in the serum of
patients with specific tumors
placental isoform (specific enzymes)
Prostate
specific antigen
(PSA) is seen in
prostate cancer
Lactate
dehydrogenase
(LDH) is seen in
hematologic malignancies
Alkaline
phosphatase
(ALP) is seen in
Metastatic carcinoma of
bone, hepatocellular carcinoma,
osteosarcoma, lymphoma, leukemia
Neuron-specific
enolase
(NSE) is seen in
neuroendocrine tumors
For LDH (sources) and ALP (liver and bone)
LDH 1 is found in
heart and red blood cells
For LDH (sources) and ALP (liver and bone)
LDH 2 is found in
white blood cells
For LDH (sources) and ALP (liver and bone)
LDH 3 is found in
lung tissue
For LDH (sources) and ALP (liver and bone)
LDH 4 is found in
white blood cells, kidney, pancreas, and lymph nodes
For LDH (sources) and ALP (liver and bone)
LDH 5 is found in
found in lover and muscles in skeleton
Serum M
protein tumor type
plasma cell dyscrasias
Serum free light chains tumor type
plasma cell dyscrasias
b2 microglobulin tumor type
hematologic malignancies
CARBOHYDRATE AND CANCER ANTIGEN TUMOR
MARKERS
CA 19-9
CA 15-3
CA 27-29
CA-125
CA 19-9, this marker is for
Gastrointestinal
cancer and
adenocarcinoma
CA 15-3 is for what tumor
metastatic breast cancer
CA 27-29 is for what cancer
metastatic breast carcinoma
CA-125 is for
ovarian cancer
Estrogen
receptor is for
breast cancer
Progesterone
receptor is for
breast cancer
Her-2/neu is for
Breast, ovarian,
gastrointestinal
tumors
Epidermal
growth factor
receptor is for
Head, neck,
ovarian, cervical
cancers
We don’t have a perfect tumor marker. Ideally, a tumor marker should be specific, not be seen on healthy individuals and readily detectable but unfortunately, we don’t have that kind of specific perfect marker, what we have are non-specific ones.
t or f
t
Majority of the tumor markers are increased not only in
malignant conditions but they might also increase in non
tumor related concerns such as __
enzymes (if there are
cellular damages).
We use tumor markers for the following purposes
o Monitoring treatment – best utilization
o Prognosis – current state of patient
o Detection of recurrence – relapse of the disease
The screening of primary hepatoma (liver carcinoma or
hepatoma cell carcinoma) in Asian countries is based on
the measurement of serum AFP
ALPHA-FETOPROTEIN (AF
First tumor marker recommended for screening for prostate
cancer in men older than age of 50.
PROSTATE SPECIFIC ANTIGEN (PSA) AND FREE PSA
The purpose was to detect prostate cancer at early curable
stages, when the tumor is still confined inside the organ
PROSTATE SPECIFIC ANTIGEN (PSA) AND FREE PSA
The most prominent are genes for susceptibility to breast
and ovarian cancer, such as ____ are now
available to screen these families for the identification of
carriers.
BRCA1 and BRCA2
are the most commonly used method to
measure tumor markers.
Immunoassays
immunnoassay
There are many advantages to this method, such as the
ability to
automate testing and relative ease of use.
determined by analyzing specimens spanning the
reportable range
linaearity
As the concentration of the particular marker increases,
the response/signal should also increase because
typically we use antigen-antibody reactions and we will
be using labelled antigen (radio or enzyme labelled
linearity
analyte concentrations exceed the analytical range
excessively and eventually will result in a false decreased
effect due to saturation of the labelled antigens which would
be affecting the reaction.
hook effect (antigen excess)
causes the actual tumor marker concentration to
be grossly underestimated
hook effect
are most commonly encountered in patients who
have been given mouse monoclonal antibodies for
therapeutic reasons or who have been exposed to mice, but
they may be idiopathic
HAMAs, human anti-mouse antibodies
____ for tumor markers can be affected by
interference from icterus, lipemia, hemolysis, and antibody
cross-reactivity
Immunoassays
is commonly used for the detection of small molecules, such
as endocrine metabolites
High-performance liquid chromatography (HPLC)
is used to detect catecholamine metabolites in
plasma and urine
HIGH PERFORMANCE LIQUID CHROMATOGRAPHY
Used to detect endocrine metabolites which may indicate
neuroblastoma, pheochromocytoma and other endocrine
related malignancies
HIGH PERFORMANCE LIQUID CHROMATOGRAPHY
meaning we’re going to exert
pressure in order to push the sample through a chamber
where there is certain pore size to effectively separate
molecules from one another.
“HIGH PERFORMANCE”
is not subject to hook effect, lot-to-lot antibody
variation, and heterophile antibodies, but is more labor
intensive and requires more experience and skill than
automated immunoassays.
hplc
Identified in tissue sections typically from a fine-needle
aspirate or biopsy samples
IMMUNOHISTOCHEMISTRY AND IMMUNOFLUORESCENCE
is a major fetal serum protein and is also one of the major carcinoembryonic proteins
AFP
Elevated in patients with primary hepatoma carcinoma cell
(HCC) and yolk-sac-derived germ cell tumors.
ALPHA FETOPROTEIN (AFP)
Most useful serum marker for diagnosis and management
of hepatoma carcinoma cell__ as elevated
level will indicate poor prognosis of the disease signaling
that the drug/therapy received is not working/effective which
is its primary function.
AFP
It is nonspecific tumor marker because it is elevated, not only in solid tumors but also in lymphoproliferative diseases
B2 – MICROGLOBULIN (B2M)
B2 – MICROGLOBULIN (B2M) normal serum level
0.9 - 2.5 mg/l
Defined first by a murine monoclonal antibody OC 125
raised against a serous ovarian carcinoma cell line.
CANCER ANTIGEN 125 (CA 125)
Useful for detecting ovarian tumors at an early stage and for
monitoring treatments without surgical restaging
CANCER ANTIGEN 125 (CA 125)
CANCER ANTIGEN 125 (CA 125) upper limit
35 U/L
> 25 U/mL are observed in patients with metastatic breast
cancer
CANCER ANTIGEN 15-3 (CA 15-3) and CA 27.29
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
CANCER ANTIGEN 15-3 (CA 15-3) and CA 27.29
pancreatic
(more significant) and gastric cancers
CA 19-9 is also related to __ substance
Lewis blood group
Useful marker for the management of patients with gastric
and colorectal carcinoma
CA 72-4
Proposed as a specific marker for tumor occurrence of
resectable gastric cancer and a prognostic marker for
survival
CA 72-4
Reported to be an independent prognostic marker for
survival in colorectal in multivariate analysis together with β
hCG and CEA
CA 72-4
Most widely used tumor marker for gastrointestinal cancer
today.
CARCINOEMBRYONIC ANTIGE
One of the circulating peptide hormones that may become
elevated in patients with increased bone turnover rate
associated with skeletal metastases
CALCITONIN
Ectopically elevated in bronchogenic carcinomas and is
also elevated in medullary carcinoma of the thyroid
calcitonin
Released by thyroid if we have a problem in calcium
concentration. Increased if we have hypercalcemia
promoting the entry of calcium in the osteocytes into the
bone (bone resorption)
calcitonin
This is not a specific indicator for carcinoma, it is just
associated with the bone and thyroid and can also increase
in conditions involving these organs.
calcitonin
Elevated serum ________ have concentrated on breast
cancer and squamous cell carcinoma of the lung
CYFRA 21-1
or cytokeratin 19 fragment
Free ___ is useful for the detection of recurrence or
metastasis for choriocarcinoma when the intact hCG may
remain normal
β-subunit
Easily detected with the use of pregnancy test kits as this
primarily detects ___
b-hCG
Used also for differentiating seminomatous and non
seminomatous type of carcinoma (male patients), detection
of trophoblastic type of tumor and for the detection of
gestational trophoblastic diseases (GTD
HUMAN CHORIONIC GONADOTROPIN
Elevated in the sera of patients with a number of different
epithelial cell cancers, including breast, lung, colorectal, and
ovarian cancers
HER2/neu (c-erbB-2) ONCOPROTEIN
Non-specific marker but have many clinical utilization
HER2/neu (c-erbB-2) ONCOPROTEINq
It is a useful marker of exocytotic sympathoadrenal activity
in patients with pheochromocytoma
CHROMOGRANIN A
Elevated if the patient has medullary carcinoma of thyroid,
and small-cell lung carcinoma
CHROMOGRANIN A
Increased serum __ levels are detected in
epithelial cancers with neuroendocrine differentiation,
including prostate, breast, ovary, pancreas, and colon
chromogranin A
Above normal in tumors originating from neural crest.
HOMOVANILLIC ACID
Useful in detection and monitoring of patients with
pheochromocytoma (adults) and diagnosis of
neuroblastoma in children
HOMOVANILLIC ACID
Can be found in tumors originating from the neuroendocrine
cell system, including glucagonomas and insulinomas.
NEURON-SPECIFIC ENOLASE (NSE)
An enzyme but is not routinely measured/tested in the lab
NEURON-SPECIFIC ENOLASE (NSE
Major protein in seminal plasma
* Significant for the detection of prostatic carcinoma
PROSTATE-SPECIFIC ANTIGEN (PSA)
Useful in monitoring squamous cell carcinomas of the head
and neck, lung, esophagus, and anal canal
SQUAMOUS CELL CARCINOMA ANTIGEN (SCCA)
