A different way in which genetic alterations can
be used in the laboratory evaluation of cancer is to
detect a genomic change that is not abnormal in
itself but which indicates a monoclonal origin of the
tumor cells. The foremost example of this is in the
evaluation of lymphoid cancer where monoclonality
is revealed by demonstrating an identical V(D)J
rearrangement in all of the cancer cells. Homogene-
ity of the immunoglobulin heavy chain gene rear-
rangement is found in tumors of B lymphocyte
lineage, and of the T cell receptor
α
or
β
genes in
tumors of T cell lineage (Scarpa and Achille 1997).
Marker substances.
The substances that serve
as markers for cancer originate in cancer cells and
enter the circulation following secretion from living
cells or release from dead cells (Figure 11.1).
Secreted substances enter the plasma directly and
distribute in the extracellular fluids. They are re-
moved by systemic processes. Substances that are
released from dead cells enter the extracellular space
in and around the tumor and are either catabolized
locally or are removed in the lymph. Lymph-borne
marker substances eventually enter the plasma,
distribute in the extracellular fluids, and are elimi-
nated. Marker substances released from cancerous
blood cells are unusual in that they have direct
access to the plasma. Marker substance concentra-
tions can be measured in any of the body fluids
transited by the marker substance. The most com-
monly studied fluid is plasma. Other fluids, such as
pericardial fluid and peritoneal fluid, are studied
when tumor involvement of the respective mesothe-
lial linings is suspected. Urine may be studied if the
marker substance or a metabolite of the substance is
eliminated by renal clearance; concentrations in the
urine are higher than in the plasma thereby allowing
for easy analyte measurement.
The concentration of a marker substance in the
plasma and extracellular fluids depends upon the rate
of entry of the substance into the fluids and its rate
of systemic elimination. Except in advanced
disease, when many body functions are compro-
mised, the systemic elimination of marker substances
is fairly constant. That means that the predominant
variable in the plasma concentration of marker
substances is the rate of entry into the body fluids.
For secreted substances, the rate of entry is deter-
mined by the individual cell rate of substance synthe-
sis and secretion and by the number of cells, i.e. the
size of the tumor. The individual cell secretion rate
usually varies from cell to cell within a tumor due to
the greater than normal degree of inter-cell pheno-
typic variability found in cancer. The rate also
varies depending upon where the cancer cells are in
their malignant evolution. Some marker substances
will be expressed in early in the evolution of the
cancer, when the cancer cells are fairly well differ-
entiated, and not later, when the cells show poor
differentiation. Other marker substances will be
expressed in poorly differentiated cancer cells and
not in well differentiated cells. Still other marker
substances will be expressed throughout the pheno-
typic evolution of the cancer.
For released substances, the entry rate is deter-
mined by the individual cell content of the marker
substance, by the number of cells, and by the
turnover rate of the cells. As with secreted marker
substances, released marker substances show
Cancer
11-4
Figure 11.1
A model of the disposition of marker substances for cancer.
local
catabolism
plasma
extracellular
fluids
systemic
elimination
lymph
PLASMA AND
EXTRACELLULAR FLUIDS
LOSS
CANCER CELLS
death
clonal
evolution
loss of markers
new markers
local
extracellular
pool
