Download Tumor Cell Markers

Chapter 3
Cancer
• Cancer is a condition of uncontrolled cellular
proliferation that knows no limits and serves no
purpose for the host. The term cancer refers to more
than 100 forms of the disease.
• For a cell to become cancerous, the following genetic
alterations must occur :
- spur cell growth;
- inactivate genes that normally slow growth;
- cells keep dividing,
- cells live on with abnormalities (no apoptosis).
- recruit normal cells to support and nourish them.
- develop strategies that prevent the immune system
from destroying them.
Physiologic Concepts
1-Cellular Differentiation
- Normal cells differentiate during development.
- Differentiation means that a given cell
becomes specialized in structure and function.
For example, some embryonic cells are
destined to become cells of the retina,
whereas others are destined to become cells
of the skin or heart.
The more highly differentiated a cell, the less
frequently it will go through the cell cycle to
reproduce and divide.
- Neural cells, which do not reproduce, are highly
differentiated cells.
- Cells that seldom or never go through the cell
cycle are unlikely to become cancerous, while cells
that go through the cell cycle frequently are more
likely to become so.
2-The Cell Clock
Normal human cells reproduce a predictable
number of times, after which they stop . This
implies that cells possess some counting system
that tells them when to stop dividing.
This system is important because if cells divided
indefinitely we would have many more cells than
is compatible with life.
Pathophysiologic Concepts
Uncontrolled Cellular Reproduction
• Cancer cells go through the cell cycle more often
than normal, resulting in an overabundance of
abnormal cells. Cancer cells spend little time in
the gap stages of interphase .
• Uncontrolled cellular reproduction occurs when
cells become independent of normal growth
control signals. This characteristic of cancer cells
is called autonomy. Autonomy results when cells
do not respond to growth inhibitors released by
neighboring cells or inhibitory growth factors and
hormones traveling in the circulation.
Anaplasia
Anaplasia refers to regression of a differentiated cell
to a less differentiated stage. Cancer cells
demonstrate various degrees of anaplasia. By
undergoing anaplasia, a cancer cell loses its
ability to perform its previous functions and bears
little resemblance to its tissue of origin. Highly
anaplastic cells may appear embryonic and begin
to express functions of a different cellular type.
Some cancer cells may become ectopic sites of
hormone production. For instance, antidiuretic
hormone (ADH) or adrenocorticotrophic
hormone (ACTH).
Tumor Cell Markers
Some cancer cells release specific substances into the
blood, urine, or spinal fluid called tumor cell
markers .
Clinical Implications of Tumor Cell Markers
1-They offer a means of identifying certain cancers,
for instance, if a specific tumor cell marker is
identified in a patient, it suggests that cancer may
exist in the person, and further diagnostic
evaluation is necessary.
2- Detects cancer's progression before, during,
and after treatment.
-If after radiation or chemotherapy the tumor
cell marker is not detectable, it suggests that
the cancer is in remission.
-If the tumor cell marker fails to decrease
during therapy or reappears in high
concentration after therapy, the tumor is
unlikely to be in remission.
Examples of Tumor Cell Markers
• Alpha-fetoprotein for liver ,ovarian and testicular
cancers.
• Carcinoembryonic antigen for colorectal cancer
• Human chorionic gonadotropin (hCG) for many
tumors, including usually cancer of the uterus
• Acid phosphatase and prostate-specific antigen
(PSA) for prostate cancer
• CA-125 is a marker for ovarian cancer.
• N.B., Failure to detect a tumor cell marker does
not mean that an individual is cancer-free.
Factors that affect tumor Growth Rate
• person's age, sex, and overall health and
nutritional status.
• The status of the host's immune system is also
important. An individual who is
immunosuppressed may be unable to recognize a
tumor as foreign.
• Certain hormonal states (e.g., pregnancy) may
stimulate certain tumor growth rates.
• stress may affect the host's ability to restrict the
development or growth of a tumor.
• location in the body and its blood supply.
• The degree of cellular anaplasia and the presence
or absence of tumor growth factors are also
important.
Descriptions of Tumor Growth and Spread
Grading: is histologic assessment of the
tumor based on the degree of anaplasia it
demonstrates. For example, poorly
differentiated (highly anaplastic) cells are
assigned a high grade.
• Staging: A clinical decision concerning the
size of a tumor, the degree of local invasion,
and the degree to which it has spread to
distant sites in a given individual.
Local Growth of a Tumor
Growing tumors kill neighboring cells by:
- compressing the cells
- blocking off their blood supply.
- Releasing chemicals or enzymes that cause the
neighboring cells to lyse and die. When neighboring
cells die, the tumor can easily grow to occupy that
space.
*To grow beyond a certain size, tumors must
stimulate the development of their own blood
supply( angiogenesis) to meet high metabolic
demands.
Metastasis
Is the movement of cancer cells from one part of the
body to another.
Metastasis usually occurs through the spread of
cancer cells from the original (primary) site in the
blood or lymph to a new, secondary site.
The term malignancy refers to the ability of a tumor
to metastasize.
Process of Metastasis
Steps involved in the metastasis of a primary tumor to a
distant site include :
1-Detachment
Cancer cells must first detach from their primary cluster. ---Normal cells detach with difficulty and if it has become
detached from its neighbors, it undergoes apoptosis.
-Cancer cells, in contrast, easily detach and begin to
enter the circulation.
2- Invasion
Detached tumor cells must gain entrance to a blood or
lymph vessel by secreting specific enzymes that attack
the integrity of the tissue.
3-Dissemination and Seeding
Movement of tumor cells in the blood or lymph is
called dissemination. Some tumor cells will get
caught in a capillary or lymph ,many cells may die, a
few tumor cells at this new site may survive and
begin to seed the area and start a new tumor
growth.
When the secondary site has reached a critical size,
the tumor cells will again begin to produce tumor
angiogenesis factor and new blood vessel formation
will be initiated to support growth of this secondary
site.
Progress of a Metastasizing Tumor
-The lungs, which receive systemic venous blood, are
the most common sites of metastasis.
- Liver is the most common site of cancers from GIT and
pancreas.
N. B., Metastasis is evaluated by observing for secondary
sites in the lymph nodes nearest to the primary site, and
then progressively further from this site.
Exceptions to this rule are tumor cells that show a striking
preference to colonize certain tissues not necessarily
downstream. The classic example of this preference is
the tendency of prostate cancer to metastasize to bone
The Immune System and Cancer
the immune and inflammatory systems have
important roles in fighting and preventing
cancer as:
-Antibodies, T cells, and natural killer (NK) cells
has been confirmed in individuals with cancer.
-Individuals who are immunocompromised,
including those with AIDS or those taking
immunosuppressant drugs, have an increased
chance of developing cancer.
Categories of Cancer
The suffix oma is usually added to the tissue term .
• Carcinoma is a cancer of the epithelial tissue,
including cells of the skin, glands, breast, cervix,
colon, rectum, stomach, pancreas, and esophagus.
• Lymphoma is a cancer of the lymphatic tissuehi.
• Sarcoma is a cancer of the connective tissue,
including cells found in the muscle and bone.
• Glioma is a cancer of the glial (support) cells of the
central nervous system.
• Carcinoma in situ describes abnormal epithelial
cells that are as yet confined to a certain area and
thus considered preinvasive lesions.
The Theory of Carcinogenesis
-Cancer development is a multi-step process that
usually requires decades to occur.
1 -The first step is mutation in the DNA during
replication . If a mistake cannot be repaired by
enzymes, the cell normally is instructed to selfdestruct.
If the DNA error is not corrected or no selfdestruction occur, the genetic change becomes a
permanent mutation and is passed on to all
daughter cells. This step is irreversible and is called
cellular initiation
2- The second step is promoting events :
interactions with endogenous and exogenous
(environmental) factors that cause additional
genetic changes leading the cell to proliferates
aggressively and without quality control.
Factors that promote the acceleration of the cell
cycle and those that allow an abnormal cell to
avoid detection by the immune system are most
likely to result in a mutated cell becoming
carcinogenic.
Promoters of DNA Replication Errors
- Certain physical agents and chemicals agents as
ionizing radiation, ultraviolet radiation,
components of cigarette smoke, aromatic
hydrocarbons, certain dyes, nitrosamines (present
in preserved meats), and asbestos.
- Certain viruses have been identified that can
cause DNA mutations as Burkitt's lymphoma,
caused by the Epstein-Barr virus, cervical cancer,
caused by certain strains of the human papilloma
virus, and liver cancer, caused by the hepatitis B
virus. Kaposi's sarcoma occurs especially in those
suffering from AIDS.
Risk Factors for cancer
1-Exposure to any physical, chemical, or viral
substance that is known to be mutagenic, and
prolonged exposure to any promoter.
2-Behavioral Risk Factors include :
- cigarette smoking and diets rich in animal fat
and preserved meats.
- exposure to asbestos, coal tar and radiation
from sunlight.
- sexual behavior
3- Hormonal Risk Factors
- Estrogen may act as a promoter for certain
cancers, such as breast and endometrial
cancer. Because estrogen levels are high in
menstruating women, the risk for developing
breast cancer is increased in women who
started menstruating early and reached
menopause late.
4- Inherited Risk Factors
Certain cancers have a higher tendency to run
in families than others. For example, colon
and breast cancer .
Protective Factors Against Cancer Development
-Women who breastfeed for at least 6 consecutive
months and who have had multiple pregnancies
have a reduced risk of breast cancer.
- Progesterone appears to be protective against
breast cancer by inhibiting the stimulatory effects
of estrogen. Progesterone is high during
pregnancy, which may explain why women who
have had many pregnancies have a reduced risk of
breast cancer.
- Vitamins A, E, and C and folic acid, are important
in reducing cancer risk. All of which are prevalent
in green, leafy and colorful vegetables and fruits.
Clinical Manifestations of cancer
-Cachexia is the general wasting of fat and
protein.
- Anemia.
- Fatigue as a result of poor nutrition, and
poor oxygenation of tissues resulting from
anemia..
Diagnostic Tools
• Screening tests, such as Pap smears to detect
cervical cancer, mammograms to detect breast
cancer, and digital examinations of the prostate.
• Blood assay for prostate-specific antigen (PSA)
and other cancer markers may be performed
based on suspicion.
• Advanced methods include radiographs, CAT
scans, and magnetic resonance imaging (MRI).
Special bone scans may also be used.
• Cancer diagnosis is confirmed by surgically
extracting a sample from a suspicious lesion, a
procedure known as a biopsy, and performing a
microscopic examination of the cells.
Complications
- Infections develop as a result of protein malnutrition,
and immune suppression .
- Pain may result of the invading tumor pressing on
nerves or blood vessels specially in space-limiting
compartments, such as bone or brain.
- Compression of the blood vessels can lead to tissue
hypoxia, lactic acid accumulation, or cell death.
-Headache is a common manifestation of advanced
brain cancer.
- bone pain is common with bone cancer at any age.
- GI pain occurs when the smooth muscle of the gut is
stretched.
Treatment
I-Surgery has a better chance of curing a cancer if
used on solid, well-circumscribed tumors.
-It may be used to relief pain or to debulk the
tumor, which reduces burden and improves the
response to chemotherapy or radiotherapy.
II-Radiation therapy uses ionizing radiation to kill
cells primarily by altering the DNA enough that
brakes on the cell cycle. Often, radiation is used in
addition to surgery to shrink the tumor.
III-Chemotherapy uses drugs to destroy
tumors which grow rapidly (most susceptible
to chemotherapy).
• However, healthy cells are also susceptible to
the damaging effects of chemotherapy.
• Chemotherapy is frequently used in addition
to surgery or radiation therapy, but may be
used alone. It also may be used for palliative
purposes.
• Chemotherapy usually causes bone marrow
suppression, which in turn causes fatigue,
anemia, bleeding tendencies, and an
increased risk of infection.
IV-Immunotherapy is a form of cancer treatment that
takes advantage of the two cardinal features of the
immune system: specificity and memory.
-Immunotherapy may stimulate the host's own
immune system to respond more aggressively to a
tumor,
- or tumor cells may be attacked by antibodies
developed in the laboratory
Cancer Prevention
- Avoidance of cigarette smoking
- A diet rich in fruits, vegetables, and fiber
and low in animal fat .
- Avoidance of sexually transmitted diseases
Cancer Detection
• Early cancer detection tests include self breast
examination and mammography, prostate
examination, self testicular examination, and
regular skin examination.
• Some screening tests, including Pap smears,
tests for intestinal polyps, and biopsies of
abnormal skin lesions.