Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

Chapter 25
Tumor Markers
Michael D. Lucroy
VCA Veterinary Specialty Center
Indianapolis, Indiana
I. INTRODUCTION
II. SERUM TUMOR MARKERS
A. Oncofetal Proteins
B. Hormones and Ectopic Hormones
C. Enzymes
D. Immunoglobulins
E. Tumor-Associated Antigens
F. Miscellaneous Serum Tumor Markers
III. FLOW CYTOMETRY
A. DNA Ploidy
B. Cell Surface Determinants
IV. PROLIFERATION MARKERS/APOPTOSIS
A. Mitotic Counts
B Thymidine Labeling Index and BrdU Incorporation
C. Nucleolar Organizing Regions
D. Proliferation Markers
E. Image Analysis
F. Apoptosis
V. IMMUNOHISTOCHEMISTRY/
IMMUNOCYTOCHEMISTRY
A. Epithelium
B. Mesenchyme
C. Drug Resistance
D. Proliferation
E. Leukocyte Markers
F. Other Markers
VI. CYTOCHEMISTRY
VII. CYTOGENETICS
VIII. MOLECULAR ONCOLOGY
IX. PROTEOMICS, GENOMICS, METABOLOMICS
REFERENCES
I. INTRODUCTION
Biomarkers, particularly tumor markers, represent an exciting
tool for the clinical discipline of oncology. However, as various
markers of disease, including physiological, biochemical,
and genetic changes, are identified, they may become more
than useful diagnostic tests. These biomarkers may also play
a role in drug discovery and development and become useful
tools for predicting the response to therapy and prognosis.
To help address the issues surrounding biomarkers and
their application to various disciplines of clinical medicine
and biomedical research, the National Institutes of Health
(NIH) formed a working group on definitions to develop a
set of preferred terms and descriptions, along with a conceptual
model, that could be broadly applied to the increasing
use of biomarkers. The working group defined a biomarker
as an objectively measured and evaluated characteristic that
is an indicator of a normal biological processes, a pathogenic
process, or a response to a therapeutic intervention
( Downing, 2000 ). The NIH Working Group on Definitions
also characterized several important applications for biomarkers
including their use for diagnosis, for staging disease,
as indicators of disease risk, and as tools to predict and
monitor clinical responses to therapy ( Downing, 2000 ).
This chapter focuses on how various biomarkers have
an application to cancer management in veterinary medicine.
Ideally, in addition to the attributes listed in the introduction,
tumor markers should be both sensitive and specific
for the detection of cancer, to minimize both false-positive
and false-negative test findings, and they should use methodology
that is minimally invasive to increase acceptance
and compliance by animal owners. Tumor markers should
also reflect the total tumor burden, identify tumor recurrence
after treatment, and be unaffected by cancer treatment
or adverse events associated with cancer treatment. Tumor
markers should be reproducible among laboratories and have
a well-defined reference range to distinguish between health
and disease. In human medicine, testing for tumor markers
is recommended only in situations where it is demonstrated
to result in a better patient outcome, increased quality of life,
or reduced overall cost of care ( Duffy, 2004 ).
The rapid technological advances in immunology, biochemistry,
and cell and molecular biology will continue to
offer new opportunities to evaluate candidate tumor markers.
However, few tumor markers, including those that are
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