MARKERS OF CANCER
Cancer can be thought of as a disease of the
body, a disease of organs, and a disease of cells
(Kahn 1994):
Since the clinical expression of cancer begins
with cellular growth, cancer has been defined
pathologically as a cellular disease. Clinicians
are also aware that cancer is a disease of
organs. Cell growth yields masses, which
then invade the organ and disrupt its function.
Cancer may also be defined as a disease
process of the body in that the body’s
response to the presence of the tumor affects
the presentation and behavior of the patient.
The usefulness of the laboratory in cancer
management must reflect an understanding of
the changes in the genes, cells, organs, and
bodily responses to cancer.
A disease of the body
The response of the body to cancer is, in large
part, mediated by cytokines released by inflam-
matory cells reacting to the cancer. Certain of the
cytokines generate a persistent acute phase response,
with its effects upon plasma proteins and circulating
blood cells, and others are responsible for the consti-
tution symptoms so typical of cancer, such as fatigue
and weight loss (Tisdale 1997). The body also
reacts to cancer by mounting an immune response to
latent and neo-antigens expressed by the cancer
cells. This contributes to the chronic inflammatory
response and can result in the development of
autoimmune disorders including a number of neuro-
logic paraneoplastic syndromes (Dropcho 1998). In
general, the activation of inflammatory and immune
responses in cancer does not produce laboratory
findings that are specific for cancer.
Other systemic consequences of cancer result
from the release of bioactive substances from
tumors. Hematologic abnormalities caused by can-
cer include cytophilias resulting from the secretion
of hematopoietic growth factors by tumors and
anemia due to the persistent inflammatory state, poor
nutrition, and bleeding. Coagulation disorders are
also frequently present in patients with cancer.
Hemorrhagic conditions are sometimes due to
thromobocytopenia, arising as an autoimmune
process, but more frequently are a consequence of
chronic activation of the plasminogen system
(Carroll and Binder 1999). Thrombotic states are
characterized by localized thrombosis and dissemi-
nated intravascular coagulation. They are caused by
the release of tissue factor and cancer procoagulant
from cancer cells (Falanga and Rickles 1999,
Gordon and Mielicki 1997) and by the thrombocyto-
sis and increased plasma concentrations of clotting
factors (especially, fibrinogen and factor VIII)
caused by the persistent inflammatory state. With
the exception of cancer procoagulant, the substances
responsible for these hematologic abnormalities are
not specific for cancer so they have little role in the
laboratory diagnosis of cancer. The laboratory eval-
uation of these processes is, however, a critical
aspect of the care of the cancer patient.
Profound systemic effects are also caused by the
hypersecretion of hormones by endocrine tumors.
Similar effects are caused by peptide hormones
secreted by some tumors of nonendocrine organs in
what are referred to as the endocrine/metabolic
syndromes of cancer (Odell 1997). In many cases of
these syndromes, the hormone that is secreted is the
normal product of a minor population of hormone-
secreting cells within the tissue of origin of the
cancer, such as the secretion of erythropoietin by
renal carcinomas. In some cases, however, the
hormone arises from a cancer in a tissue that is not
believed to contain cells that elaborate the hormone,
such as the secretion of erythropoietin by cerebellar
hemangioblastomas. It is possible that in tumors of
this sort, the hormone is expressed as a normal
paracrine cytokine within the organ and that it
assumes the status of a hormone simply by its
overexpression by the tumor (Odell 1997).
A disease of organs
Cancers generate masses of tumor cells that dis-
place and compress neighboring normal tissue
leading to injury of the tissue and loss of tissue
function. The extent of the effects on the nearby
Cancer
11-1
Chapter 11
CANCER
© 2001 Dennis A. Noe
