tissue depend, in part, upon the size of the tumor.
While still small, tumors tend to have little or no
effect upon the surrounding tissue. As they grow in
size, they affect a greater and greater amount of
normal tissue. Even more important than size
though is location. Cancers that are positioned to
collapse or obstruct a tubular structure or large
vessel will produce effects long before a tumor
growing far from any vital structure. For instance,
because it produces obstruction, a squamous carci-
noma of the bronchus will cause much more in the
way of clinical effects than a comparably sized
adenocarcinoma in the periphery of the lung.
Another determinant of the extent of the effects
of a tumor upon the surrounding tissue is the patho-
biologic stage of the tumor. Before a cancer has
begun to spread, all of its local effects are due to the
volume of space it occupies. Once it becomes
invasive, cancer cells infiltrate normal tissue, dis-
rupting the parenchymal microarchitecture and ob-
structing the microvasculature. This is very injuri-
ous to the normal tissue and inevitably leads to an
accelerated loss of tissue function. When a cancer
becomes metastatic, it spreads to regional lymph
nodes, where it causes local mass effects, and to
distant sites, where it causes injury and loss of
function in the seeded organs.
The interplay of tumor location and pathobio-
logic state is well illustrated by prostate cancer.
Most prostate cancers arise in the posterior portion
of the prostate, away from the urethra, and expand
without causing any obstructive symptoms. If they
are not detected early by clinical screening proce-
dures, they will become invasive within the pelvis,
in which case they can cause bladder dysfunction,
ureteral obstruction with hydronephrosis, and local
nerve and blood vessel damage usually manifesting
as impotence. Prostate cancer can present with
symptoms of metastatic disease if the tumor metasta-
sizes early and the local spread has not produced
symptoms. Bone pain, lymphadenopathy, and con-
stitutional signs of cancer, most notably weight loss,
constitute the usual symptoms of metastatic disease.
In contrast, those cancers that develop more anteri-
orly tend to cause symptomatic urethral obstruction
early in their evolution, often before they are widely
invasive or metastatic.
Because of interindividual variability in the time
course and pattern of tissue injury and function loss
caused by tumors, markers of injury and function
have a limited role in the diagnosis of cancer.
Function markers are extremely useful, though, in
providing quantitative indices of the functional status
of involved organs.
A disease of cells
Cancer cells differ from normal cells in an
immense number of ways, many of which are of
central importance in the study of the biology of
cancer (Hanahan and Weinberg 2000). Those dif-
ferences that are clinically measurable can be used as
cellular markers of cancer. These markers can be
placed into two broad categorizes. The first
category consists of markers that are present as
components of whole cells. The laboratory mea-
surement of these markers requires a cell sample.
The second category consists of marker substances
that are present in the body fluids as a result of
having been secreted by living cancer cells or
released from dead cancer cells. These markers are
measured in body fluids, most often in plasma, and
do not require access to a cell sample.
Cancer cells.
Cancer cells are identified by
studies of cellular phenotype and cellular genotype.
Of the studies of phenotype, the characterization of
morphology by microscopy is the most important. It
remains the most specific of all laboratory markers
of cancer. For this reason, the microscopic exami-
nation of cells or tissue obtained by biopsy of a
tumor is considered essential for the diagnosis of
cancer. Morphologic characteristics of interest in-
clude the cytologic features of individual cells, the
microarchitecture of the cell population, and the
invasion of normal tissue by the cells. Biopsy
techniques that provide tissue specimens usually
allow all of these characteristics to be evaluated.
The cytologic features of some cancers are highly
specific and allow for the diagnosis of cancer based
on the examination of cells obtained by scrape or
aspiration biopsy.
Genetic abnormalities are frequently demonstra-
ble in cancer cells (Table 11.1). Many of the abnor-
malities that have been found are present so
consistently among tumors of the same type that they
probably represent genetic changes involved in the
inception and malignant progression of that tumor
type (e.g., Ried
et al.
1996). Large-scale structural
abnormalities of the chromosomes such as deletions
and translocations can be studied by chromosome
analysis (see Chapter 10). Chromosome analysis by
G-banding is performed on tumor cells taken directly
from biopsy material or on tumor cells grown in
Cancer
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