microscopic appearance of a tumor but, occa-
sionally, it is necessary to perform special studies in
order to make an assignment as to the cell type
(Table 11.3). Electron microscopy can be used to
extend the resolution of the microscopic examination
and special stains can be employed to identify certain
cellular contents. Cell-type specific enzymes can be
detected by enzyme histochemistry and enzymes and
other proteins can be demonstrated by immunocyto-
chemistry. Characteristic chromosomal abnormali-
ties can be detected by microscopic techniques such
as fluorescence in situ hybridization (FISH) or by
molecular biologic analysis, such as Southern blot
hybridization or polymerase chain reaction (PCR).
Chromosomal abnormalities have proven to be
especially useful markers in the classification of
hematologic malignancies (Frizzera
et al
. 1999).
Among solid tumors, the t(11;22) translocation of
Ewings sarcoma has been found to be a reliable
classification marker.
MANAGEMENT
The management of a patient with cancer
includes establishing a prognosis, selecting appropri-
ate therapy, and clinical monitoring. Markers of
cancer are used in all of these aspects of care.
Prognosis and prediction
In cancer medicine, prognosis can be thought of
as an expression of the probability that the cancer
will progress. This probability is usually expressed
as the likelihood of progression within a specific
period of time, say a certain number of years.
Obviously, for many tumors, the prognosis depends
upon whether therapy is undertaken; it is possible
for the prognosis of the untreated cancer to be
dismal while the prognosis with treatment may be
good. To account for the effects of therapeutic
intervention on prognosis, the concept of prediction
has been developed. Prediction is the probability
that the cancer will respond to a specified therapy.
Prognosis depends largely upon the type of
cancer and upon the extent and location of spread of
the cancer at the time of presentation. These and
other features of a cancer that relate to the prognosis
in individual patients are referred to as prognostic
factors. Prognostic factors that relate to the type of
tumor include histopathologic attributes that corre-
late with tumor proliferation rate, aggressiveness, or
metastatic potential; genetic alterations that relate to
the stage of malignant evolution of the cancer; and
cell and marker substance findings that relate to
phenotypic features of the cancer associated with
disease progression. The extent of spread of a
cancer is assessed from clinical examination, tumor
biopsy or surgical removal, and imaging studies.
Prognosis usually worsens in the order: in situ
cancer, tumor confined to the organ of origin, local
spread of tumor beyond the organ of origin, involve-
ment of regional lymph nodes, and distant metastatic
spread. The prognostic importance of each of these
categories varies somewhat among cancer types as
does the prognostic implication of the exact extent of
intra-organ and local spread. As an aid to the clini-
cian, staging systems have been devised that list the
varying criteria of tumor spread and order their
importance. The most popular of these are the TNM
(
T
umor
N
ode
M
etastasis) staging systems. A crucial
use of staging designations beyond that of establish-
ing a prognosis is to aid in identifying patients in
whom the extent of tumor spread is such that
Cancer
11-15
Table 11.3
Cell type-specific Cellular Constituents of Use in the Classification of Cancer
Cellular constituent
Technique
Example
Cancer
Membrane protein
immunocytochemistry
leukocyte common antigen lymphoma, lymphocytic leaukemia
Secretory granules,
electron microscopy
premelanosome
melanoma
granule contents
Cytoskeletal protein electron microscopy
desmosomes
squamous carcinoma
Cytosolic enzyme
enzyme histochemistry
chloroacetate esterase
acute myelogenous leukemia
Cytosolic protein
immunocytochemistry
myoglobin
rhabdomyosarcoma
Chromosomes
FISH
t(11;22)
Ewings sarcoma
PCR
Southern blot hybridization
