Download Basic Oncology 2016 - American College of Osteopathic Internists

The American College of Osteopathic Internists
Internal Medicine Board Review Course 2016
Basic Oncology
Kevin P. Hubbard, DO, MACOI
ACOI 2016
Basic Oncology
Definition
Type to enter text
Basic Oncology
The terms cancer, neoplasia, and malignancy are usually used interchangeably. The
disease called cancer is best defined by four
characteristics:
Clonality: Cancer originates from a single stem cell which proliferates to form a
clone of malignant cells.
Autonomy: Growth is not properly regulated by normal biochemical and physical
influences in the environment.
Anaplasia: There is a lack of normal,
coordinated cell differentiation.
Metastasis: Cancer cells develop the
capacity for discontinuous growth and
dissemination to other parts of the body.
The process by which a normal cell is converted into one which exhibits these characteristic traits is termed malignant transformation.
Cancer Statistics
One-third of all individuals in the United
States will develop cancer. The estimated annual incidence of cancer in this country is over
1.7 million cases. The 5-year relative survival
rate for these patients (the probability of escap-
ing death from cancer) for 5 years following
diagnosis has risen to over 50% as a result of
progress in the early diagnosis and the therapy
of this disease. However cancer remains second only to cardiac disease as a cause of
death in this country.
Twenty percent of Americans die from cancer and this amounts to over 570,000 cases
per year. Over half are due to the four most
common types of cancer…lung, breast,
prostate, and colorectal. Over the past 10
years of available data (2000-2010), cancer
death rates have declined by more than 1%
per year in men and women of every racial/
ethnic group with the exception of American
Indians/Alaska Natives, among whom rates
have remained stable.
Lung cancer occurs most commonly in
males.
Breast cancer is the most frequent cancer in females, but lung cancer ranks as
the number one cause of cancer death
among women.
Cancer of the colon and rectum occurs
with equal frequency in both males and
females.
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Cancer is more common in urban
dwellers, and in the economically disadvantaged.
Karyotypic Abnormalities
Expression of cellular characteristics usually occurs under well coordinated control. In the
case of malignancy, the normal control process
is subverted or bypassed from anomalous activities of a select group of genes
("oncogenes"), which have central importance
to the regulation of cellular activities. It is believed that multiple insults to the genetic information are required for malignant degeneration
(the "multi-hit" hypothesis). Indeed, as malignant cells grow and dedifferentiate, multiple
genetic aberrations are seen; metastatic lesions
may have significant chromosomal alterations.
Additionally, loss of function of tumor suppressor genes (also known as "antioncogenes")
may be responsible for the development of
certain tumors.
Clonality
Virtually all solid tumors and a majority of
hematopoietic malignancies display cytogenetic abnormalities which are inherited by the
population of tumor cells. These anomalies
may involve translocations of chromosomal
fragments to new locations, as well as additions or deletions of parts of chromosomes or
whole chromosomes.The best and most well
known karyotypic abnormality is the Philadelphia chromosome (Ph) observed in more
than 95% of patients with chronic myelogenous leukemia (CML) in which the long arm of
chromosome 22 is translocated onto the long
arm of chromosome 9. Characteristic chromosomal rearrangements are described in a number of other human cancers.
Autonomy
A variety of experimental assays document
the capacity of the malignant cells to continue
to proliferate under normally nonconducive
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conditions. Many tumor cell lines can proliferate
in culture medium without the usual requirement for serum, provided that a "cocktail" containing three to five essential growth factors
and other growth promoting agents is added.
Malignant cells may obviate the requirements
for even these essential factors.
Autocrine secretion
This involves production of a growth factor
(or its analogue) by tumor cells. In this situation
a gIycoprotein secreted by the tumor cells may
have the capacity to bind to a receptor on the
surface of the tumor cells resulting in autostimulation. In other situations, the tumor cell may
activate an internal biochemical process ordinarily dependent upon binding of a specific
growth factor to a cell surface receptor, completely bypassing the need for the growth-promoting agent.
Anaplasia
Defined as a lack of normal differentiation,
anaplasia is a useful characteristic in the pathologic diagnosis of malignancy. Most cancer
cells usually bear some of the morphologic
characteristics of their normal mature counterparts, but also display cellular and histologic
abnormalities readily detectable with the light
microscope. The cells tend to have large nuclei
with more apparent chromatin and prominent
nucleoli. There are increased mitoses, as well
as abnormal mitoses and giant cells containing
multiple nuclei reflecting failure of karyokinesis.
The histologic appearance is one of disarray,
with partial or complete loss of normal tissue
architecture. Partial formation of structures
such as glands or villi may be suggested, even
in poorly differentiated malignancies. The degree of abnormal morphology usually correlates
with the extent of disease spread. Histologic
features which are abnormal but do not meet
the criteria of anaplasia (loss of differentiation)
are designated dysplastic. These changes may
be seen in premalignant situations; for example, in the epithelial lining of the bronchi of cigarette smokers. These abnormalities are often
reversible as cessation of smoking can lead to
normalization of the lung epithelium over a period of several years.
Although the term is not used this way, the
process of anaplasia may be expressed at a
biochemical level as production of hormones or
hormone-related peptides which are
either
improperly regulated by normal feedback
mechanisms (e.g., excessive corticosteroid
production in adrenal carcinoma), or are not
appropriate for the particular cell type if it were
normally differentiated (e.g., ACTH production
by a carcinoma of the lung). In such cases, the
genomic repertoire of the malignant cell is expressed inappropriately.
Metastasis
Malignant cells lose their adherence and
restrained position within an organized tissue,
move into adjacent sites, develop the capacity
both to invade and to egress from blood vessels, and become capable of proliferating in
unnatural locations or microenvironments.
Changes in growth patterns are accompanied
by biochemical alterations which have the capacity to promote the metastatic process. Invasive tumors may secrete a variety of tissuedegrading enzymes including collagenases and
lysosomal hydrolases. Plasminogen activators
which lead to promotion of fibrinolysis are also
produced. Conversely, procoagulant compounds may be released into the environment
of the tumor cells at stages when focal aggregation of cells might be of survival value. In experimental situations where tumor cells show a
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propensity to select a particular organ as a preferred site of metastasis, surface molecules on
the metastatic cells appear to have a high affinity for endothelial cells in the vasculature of the
specific target organ (the "seed and the soil"
hypothesis). Multiple biochemical steps are
involved in the progression of a tumor from a
homogeneous proliferating clone to a group of
heterogeneous subpopulations of cells, some
of which have progressively accumulated the
entire array of enzymes and surface molecules
required for metastasis. Developing metastatic
potential appears be a relatively late step in the
genetic cascade leading to clinically relevant
cancers, which would account for late metastases associated with some large tumors of
certain histologic subtypes. Interfering with the
ability of cancer cells to migrate has therapeutic
implications. It may be for this reason that the
rate of metastasis is low during early tumor
growth, in spite of the well-documented fact
that malignant cells are often released from a
tumor into the circulation continuously and in
large numbers.
Biology of Tumor Growth
There are three general classes of normal
tissue with regard to growth characteristics:
Renewing (marrow and germ cells).
Cells in this population have a finite, usually short, life span, and continued replacement from a stem cell pool normally
takes place.
Expanding (liver, kidney, and endocrine
glands). Mitotic potential becomes apparent in cells only when cell loss takes
place (trauma, surgical resection), and
then the tissue is replenished.
Static (neurons and striated muscle). The
cells live for the duration of the life of the
host and are normally not replaced if lost.
Growth characteristics are best described
as a Gompertzian function: as the mass increases, the growth is matched by exponential
retardation of growth.
Growth curve demonstrating Gompertzian kinetics.
Karyotypic Abnormalities
Expression of cellular characteristics usually occurs under well coordinated control. In the
case of malignancy, the normal control process
is subverted or bypassed from anomalous activities of a select group of genes
("oncogenes"), which have central importance
to the regulation of cellular activities. It is believed that multiple insults to the genetic information are required for malignant degeneration
(the "multi-hit" hypothesis). Indeed, as malignant cells grow and dedifferentiate, multiple
genetic aberrations are seen; metastatic lesions
may have significant chromosomal alterations.
Additionally, loss of function of tumor suppressor genes (also known as "antioncogenes")
may be responsible for the development of
certain tumors.
Genetic Factors
For many of the common malignancies,
the incidence of cancer is higher among patients with positive family histories than among
unselected patients. The risk can rise to as high
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as twenty-five to thirty-fold in certain groups of
patients with a familial history of breast cancer
or bowel cancer. Hereditary neoplasms may
occur as the only manifestation of a gene defect or as part of a generalized syndrome involving multiple developmental abnormalities.
The inheritance patterns in these disorders are
generally autosomal dominant, with varying
penetrance. Half of the children of patients with
these disorders will inherit the gene defect.
Another group of individuals with what are
termed preneoplastic syndromes have been
described by Fraumeni. They are divided into
four varieties:
Hamartomatous syndromes (phakomatoses)
Includes neurofibromatosis, vonHippelLindau syndrome, tuberous sclerosis,
Cowden's syndrome, Peutz-Jeghers
syndrome, and multiple exostosis syndrome.
Neurofibromas undergo sarcomatous
changes in about 10% of patients, with
development of gliomas in the brain or
optic nerve, meningiomas, acoustic neuromas, or pheochromocytomas.
The other members of this group will undergo malignant degeneration to form
sarcomas or carcinomas in 5-20% of
patients at some time in their life.
Genodermatoses
Includes xeroderma pigmentosum, albinism, Werner's syndrome, epidermodysplasia verricuformis, dyskeratosis
congenita, and polydysplastic epidermolysis bullosa.
Rare autosomal recessive genetic disorders which conspicuously involve the
skin.
Chromosome breakage disorders
Includes Bloom's syndrome and Fanconi's syndrome.
Characterized by the recessive inheritance of chromosomal instability and rearrangements of karyotypes; patients
have an increased incidence of acute
leukemia.
Hereditary immune deficiency syndromes
Includes ataxia telangiectasia, WiskottAldrich syndrome, late onset immune
deficiency, and X-linked agammaglobulinemia.
These patients have an increased incidence of neoplasia, most commonly the
lymphoproliferative malignancies.
Family Cancer Syndromes
Li-Fraumeni Syndrome (or SBLA Syndrome)
Rare autosomal dominant syndrome predisposing individuals to a variety of malignancies, including soft tissue sarcomas, breast cancer, brain tumors,
leukemias, lung cancer, and adrenocortical carcinomas.
Lynch Syndrome
Autosomal dominant disorder which predisposes individuals to nonpolyposis carcinomas of the colorectum (Lynch I). Additionally, the association of colorectal
cancer with carcinomas of the breast
(Lynch II), endometrium, and ovary exists.
Radiation
Less than 3% of cancers result from exposure to radiation. Radiation that can remove
electrons from atoms is called ionizing radiation. Sources include electromagnetic waves
(x-rays and gamma rays), and charged parti-
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cles such as protons. Information on the capacity of radiation to induce cancer in humans
comes from atomic bomb blasts, on individuals
accidentally exposed to irradiation or radiative
fallout, and on patients exposed to radiation for
diagnostic purposes or for therapy.
Exposure to the aerosol caused by radon
daughters (predominantly in uranium miners)
increases the risk of malignancy in exposed
tissues (most often lung). Radon daughters are
α-particle emitters which can directly damage
DNA. Individuals in ground-level dwellings are
also at risk.
Nearly all tissues are susceptible to tumor
induction by radiation, but most sensitive are
the bone marrow, breast, and thyroid. The latent period is only 2 to 5 years for acute
leukemia, and 5 to 10 years for solid tumors.
There is a higher incidence in those who have
received radiation therapy for neoplastic diseases and for ankylosing spondylitis, and of
thyroid cancer in children irradiated for thymic
enlargement.
Solar radiation resulting from exposure to
electromagnetic radiation from the sun is the
primary risk factor in skin cancer. Skin cancer is
rare in blacks and the deeply pigmented racial
groups, whereas it is especially common in faircomplexioned individuals. It occurs primarily on
the parts of the body exposed to sunlight and
has a higher incidence in outdoor workers. Patients with genetic diseases such as xeroderma
pigmentosum and albinism, which are exacerbated by sunlight, are at high risk for the development of skin cancer. The carcinogenic effect
of solar irradiation is highest in the spectral
range of 290 to 320 nm (UV-B radiation), causing delayed erythema in human skin (sunburn).
This range of wavelengths correlates with the
action spectrum for UV-induced damage to
DNA.
Exposure to solar ultraviolet irradiation is
also a risk factor in melanoma. As with skin
cancer, there is a higher incidence of
melanoma among populations living at a latitude nearer the equator where exposure to UV
irradiation is greatest. Risk is cumulative with
continued sun exposure, and increases dramatically for those who have a history of 3 or
more blistering sunburns.
Tobacco
The principal carcinogenic agent in our
environment is inhaled tobacco smoke. Lung
cancer is more than tenfold higher in male
smokers than in nonsmokers. Tobacco smoking is associated with increased rates of cancer
of the oral cavity, esophagus, kidney, bladder,
and pancreas. Particulate matter known as tar
contains a long list of chemicals, primarily polycyclic hydrocarbons, which have been shown
experimentally to be contact carcinogens. The
metabolic activation of tobacco components
such as the cyclic N-nitrosamines can produce
carcinogens with the capacity to act upon the
cells of internal organs.
Tobacco-related malignancies account for
one-third of all cancer deaths among men in
the United States and for 5 to 10 percent of all
female cancer deaths. As a result of increased
use of tobacco by women in the period since
World War II, the incidence of lung cancer
deaths in females has surpassed that of breast
cancer.
Smoking cessation results in a gradual decrease in risk, though the risk for reformed
smokers is still greater than risk for those who
never smoked.
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Occupational Exposure
The first report of cancer related to occupational hazards was Percival Pott's observation of an unusually high frequency of scrotal
cancer among London chimney sweeps in
1775. It is now known that skin cancer (including scrotal) can be induced by a variety of coal
tar products, such as the materials contacted
in the London chimneys. Epidemiologic studies
also have related lung cancer to exposure to
coal byproducts.
A number of other compounds have been
demonstrated to be carcinogenic including arsenic (lung, skin, and liver cancers), asbestos
(mesothelioma, lung cancers), benzene
(leukemia), benzidine (bladder cancer), chromium compounds (lung cancers), mustard gas
(lung cancer), polycyclic hyrocarbons found in
coal byproducts (lung and skin cancers), and
vinyl chloride (angiosarcoma of liver).
Air pollution
Lung cancer incidence is increased by tobacco smoking and by certain industrial and
occupational exposures (primarily related to
coal tar and combustion by-products). Once
the risks resulting from exposure to the above
factors are taken into account, the epidemiologic evidence that links ambient air pollution to
lung cancer remains inconclusive, although a
recent British study was able to directly link
pollution in urbanites to an increased cancer
risk. Studies relating the incidence of lung cancer to increased levels of polycyclic hydrocarbons and benzo(a)pyrene in urban air are complicated by the difficulty of eliminating the exposure to these compounds through tobacco
smoking as well as occupational exposure.
Medications
Estrogens
The synthetic nonsteroidal estrogen diethylstilbestrol (DES) causes an increased incidence of vaginal and cervical cancer in daughters who were exposed in utero. Conjugated
estrogens have been shown to increase the
incidence of endometrial cancer in patients
treated for menopausal symptoms. The use of
progesterone concomitantly, along with a decreased estrogen dose, may obviate this problem.
Chemotherapeutic agents
Alkylating agents have been shown to
cause an increased incidence of acute myelocytic leukemia and probably other malignancies. Tamoxifen can increase the likelihood of
uterine cancer in women using the product.
Patients taking inhibitors of the BRAF kinase pathway (utilized in melanoma and renal
cell carcinoma) may develop keratoacanthomas or squamous carcinomas of the skin.
The pathophysiology is activation of the mitogen-activated protein (MAP) kinase pathway.
Approximately 25% of all patients on BRAF
kinase inhibitors develop these cancers, which
are managed locally per standard treatment;
the development of these cancers does not
require discontinuation of the medication.
Immunosuppressives
Recipients of organ transplants who are
treated with immunosuppressive agents, such
as azathioprine and prednisone, have an increased incidence of large cell lymphoma as
well as a variety of solid tumors.
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Increased incidence of a variety of malignancies (Kaposi's sarcoma, CNS lymphoma,
and others) is observed in individuals with inherited and acquired immunodeficiencies. This
has been attributed to reduced immune surveillance, but a variety of other explanations are
equally likely, such as activation of a latent
oncogenic virus or chronic immunostimulation
in conjunction with a compromised and malfunctioning immune system.
Medications as cancer preventatives
Some data support the association of nonsteroidal antiinflammatory drugs (NSAIDS) and
aspirin in reducing the risk for development of
colon cancer. Patients taking these medications had a lower incidence of colorectal cancer than untreated controls and endoscopic
regression of colon polyps (? drug mediated
differentiation) has been documented. The
same is true for patients taking supplemental
calcium.
Celecoxib (Celebrex®) is FDA approved
for treatment of familial colonic polyposis syndromes, along with traditional treatment. Adenomatous polyps produce COX-2 which may
explain the activity of the drug.
Evidence from two breast cancer prevention trials suggests tamoxifen (Nolvadex®)
and raloxifene (Evista®) have a major impact
in decreasing risk of breast cancer.
Diet
Evidence directly correlates the intake of fat
with cancer at several sites, especially the
breast and colon. Explanations include:
Increased adiposity leading to greater
conversion of androstenedione to estrone, which could i n fl u e n c e c a rc i n ogenesis in the breast.
Stimulation of increased bile salt excretion which could alter gut flora and thereby augment the production of carcinogenic substances by the bacteria in the
colon.
Vitamin C may act to prevent cancer by
blocking endogenous formation of N-nitroso
compounds in the gastrointestinal tract. Vitamin E and selenium are antioxidants, but no
clear indication that vitamins or trace elements
prevent cancer in humans.
Dietary fiber enhances the rapid transit of
potential carcinogens through the colon, which
could explain the low incidence of bowel cancer and rectal cancer in tropical Africa. The
data supporting this hypothesis have recently
been called into question. The accumulated
scientific evidence does not support the anticarcinogenic value of particular vitamins, minerals, or nutritional supplements in amounts
greater than provided by a prudent diet.
Analogs of Vitamin A have been shown to
work as differentiating agents in leukemia and
to reduce the incidence of secondary malignancies of the head and neck. Vitamin A
analogs may also have a role in the treatment
of carcinomas of the cervix and vagina.
Viruses
Human T cell Lymphotropic Virus type 1
(HTLV-1)
HTLV-1 is a retrovirus associated with T cell
lymphoma. It is also implicated in cutaneous T
cell lymphomas (mycosis fungoides) and acute
T cell leukemia.
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Epstein-Barr virus (EBV)
EBV is closely associated with African
Burkitt's Iymphoma. The viral genome can be
isolated in malignant cells of nasopharyngeal
carcinoma. Cofactors in the development of
these malignancies might be holoendemic
malaria in African Burkitt's lymphoma, and a
particular configuration of histocompatibility
antigens in the case of nasopharyngeal carcinoma among Chinese.
Hepatitis B virus (HBV)
HBV infection is strongly linked with the
incidence of hepatocellular carcinoma. The viral
genome inserts near (and may activate) the cmyc protooncogene. Chronic active hepatitis
due to HBV might predispose to carcinogenesis in these cells. There may be a variety of
contributing factors, including malaria, malnutrition, and exposure to aflatoxin.
Hepatitis C virus (HCV)
Approximately one-third of all cases of hepatocellular carcinoma in the United States
develop as a result of hepatitis C infection. The
cases appear to develop almost exclusively in
those with chronic infection who develop cirrhosis.
Herpes simplex virus (HSV)
There is a statistical correlation between
HSV-2 viral infection, which is sexually transmitted, and the incidence of cervical cancer.
Human papilloma virus (HPV)
There is a strong correlation between HPV
infection and cancers of the labia, vagina,
cervix, penis, and anus. The virus has also
been linked to squamous cancers of the head
and neck. Two vaccines are currently in use
with the hope of reducing the incidence of
HPV-induced cancers of these sites. The vaccines must be administered prior to HPV exposure, as they do not help address existing HPV
infections.
Oncogenes
Oncogenes are defined as genetic material
which, when altered, causes formation of cancer.
Definitions…
Protooncogene—a presumably normal
gene which may be a target for carcinogenic agents. Not causative of cancer by
itself in an inactive form.
Oncogene—the active cancer gene; an
“activated protooncogene”.
Antioncogene—a gene which prevents
the formation of a given malignancy. Also
known as “tumor suppressor” gene.
Function (and malfunction) of protooncogenes
and oncogenes
The growth and division of a normal cell
residing in a tissue is controlled almost exclusively by its surroundings. All cells have a complex machinery that enables it to receive
growth signals from surrounding tissue,
process the information, and initiate a growth
response.
Protooncogenes encode many of the proteins in this complex machinery. Oncogenes
participate in this signaling mechanism by
specifying aberrantly functioning versions of the
components of this circuitry. The proteins then
cause the cell to grow and divide, even when
the growth factors from its surroundings are
absent.
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More recently, data have emerged demonstrating an insensitivity for colorectal cancers
expressing codon 12 or 13 K-RAS mutations
to irinotecan or panitumumab. Evaluation of
colorectal carcinomas for K-RAS mutations is
becoming a standard methodology in all cases
diagnosed in the United States.
Genomic studies are in early development
that will allow physicians to evaluate cancers in
an attempt to identify patients who may have
more aggressive disease. The assay involves
screen the cancer genome for the presence of
20-30 genetic markers known to affect cell
growth, proliferation, and metastasis. With this
information, it may be possible to identify patients who will benefit from targeted therapies
and to identify patients in advance for whom
adjuvant therapy may not be beneficial. This
approach allows for the tailoring of treatment to
best suit the needs of the individual patient,
rather than depending on statistical approaches from population-based studies.
Antioncogene function
These are genes that decrease the likelihood of developing a given malignancy. The
earliest example is the retinoblastoma (RB)
gene. Normally present in two copies per cell, it
was found that normal cell growth and differentiation is not affected if one RB gene is inactivated; when both RB genes are inactivated, the
risk of developing retinoblastoma increases
dramatically. Only one copy of the gene is active, providing a margin of safety if one gene in
a cell becomes inactive or damaged. Unfortunately, inactivated genes can be passed from
parent to offspring, thus removing this safety
margin—a child who inherits one intact and
one defective RB gene has a 90% chance of
developing a retinal tumor by age 7.
Tumor Markers
Tumor markers are abnormalities which are
(hopefully, but not usually) specific for a particular type of malignancy. Often, the term marker
is used in a more restrictive sense, referring to
molecules which are produced in abnormal
amounts or under abnormal circumstances and
are released into the circulation. Assays of
markers may be of great help to the clinician in
a number of ways:
Screening of high-risk individuals for the
presence of malignancy.
Assistance in the diagnosis of malignancy. No tumor marker is 100% specific for
a given malignancy!
Monitoring of the effectiveness of therapy.
Detecting early recurrence.
Detect metastases by immunologic
means. The tumor marker of greatest use to the
clinician is human chorionic gonadotropin
(HCG), which has specificity because of its
nearly exclusive production by the trophoblastic
epithelium of the placenta under normal circumstances. The hormone also may be secreted by trophoblastic tumors, as well as
germ cell neoplasms of the testes and ovaries.
The usefulness of the assay for HCG is
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markedly enhanced by clinical data which
show that changes in the serum HCG concentration in patients with secreting trophoblastic
malignancies accurately reflect changes in the
tumor burden. Therefore, decisions on the appropriate time to discontinue therapy can be
based on the time course of serum levels, and
decisions to reinstate therapy for recurrent disease are made on the basis of reappearance of
HCG in the serum. The clinical test for HCG
utilizes a radioimmunoassay for the beta subunit, to avoid cross reactivity with luteinizing
hormone.
Oncofetal antigens
Two clinically useful tumor markers are
products of genes which are expressed during
the normal differentiation of fetal tissue but are
partially or completely suppressed in the adult.
These markers have been termed oncofetal
antigens.
Carcinoembryonic antigen (CEA) is a nonspecific tumor-associated antigen that may be
elevated in a variety of benign conditions, such
as cigarette smoking, chronic pulmonary disease, aIcoholic cirrhosis, hepatitis, and inflammatory bowel disease. In the presence of malignancy, CEA concentrations may be eIevated
in the blood and other body fluids. Serum levels of CEA above the normal concentration of
2.5 ng/mL are found in greater than 50% of
neoplasms involving the colon, pancreas,
stomach, lung, and breast. CEA is not selective
for cancer, and measurements of its levels
should not be used in screening for the presence of malignant disease. Serial measurements of CEA levels in patients with secreting
malignancies can provide valuable information
on the efficacy of treatment and the recurrence
of disease.
Alpha fetoprotein (AFP) is produced by the
liver and gastrointestinal tract epithelium during
gestation. It is elevated in 70% of patients with
hepatocellular cancer, the majority of patients
with nonsemanomatous germ cell cancers, and
occasional patients with neoplasms of the GI
tract. As with CEA, the serum concentration
may be elevated in some benign conditions,
especially in inflammatory disease of the liver.
Its utility is in monitoring tumor activity, especially in the case of testicular tumors.
Carbohydrate-associated antigens
These markers represent glycoprotein moieties released into the serum in the face of malignancy. They probably have better specificity
than the oncofetal antigens, but not 100%
specific as they are elevated in benign states
as well:
CA125—elevated in gynecologic malignancies (ovary, endometrium), some gastrointestinal malignancies (pancreas).
CA19-9—elevated in pancreatic carcinoma, some biliary carcinomas, and occasionally in islet cell tumors.
CA27.29—marker for breast cancer. Can
be elevated in a wide variety of other malignancies as well.
Other biochemical markers
Calcitonin—familial medullary carcinoma
of the thyroid.
Prostate specific antigen (PSA)—prostate
cancer. It may also be elevated in the
presence of benign prostatic hypertrophy.
Levels of PSA are not significantly affected by digital rectal examination.
Insulin or gastrin hypersecretion—islet
cell tumors.
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References
deVita VT, Lawrence TS, Rosenberg SA, eds., Cancer: Principles and Practice of Oncology,
9e ed., Philadelphia: JB Lippincott Co. 2011.
Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J, eds., Harrison’s Principles of Internal Medicine Online Textbook and Text, 18e Ed., New York: McGraw-Hill Inc.
2012.
Tumor Marker Fact Sheet. National Cancer Institute 2011. http://www.cancer.gov/cancertopics/factsheet/detection/tumor-markers
Edge SB, Byrd DR, Compton CC, et al.; AJCC Cancer Staging Manual, 7th edition; 2009;
Springer.
DeSantis C, Siegel R, Jemal A; Cancer Facts & Figures 2016. Atlanta: American Cancer
Society; 2016.
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