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

III. Flow Cytometry
755
cancer of the gastrointestinal tract and nonneoplastic diseases
such as endometriosis. CA-125 has not found application in
veterinary medicine.
2 . Prostate-Specifi c Antigen
Prostate-specific antigen (PSA) is a tumor-associated
antigen identifiable in the serum of men with prostate
cancer, and it has become a widely used tumor marker for
prostate cancer screening programs. Evidence suggests
it may not adequately discriminate between cancer and
benign enlargement of the prostate gland ( Constantinou
and Feneley, 2006 ). One study failed to identify PSA in
canine serum, although weak immunoreactivity was noted
on immunohistochemistry of canine prostatic adenocarcinoma
specimens ( Bell et al. , 1995 ).
3 . Other Tumor-Associated Antigens
Tumor-associated antigens, 1A10 and SB2, have been identified
in the serum of dogs with a variety of cancers with
the use of murine monoclonal antibodies developed against
a canine mammary carcinoma cell line ( Wang et al. ,
1995 ). However, the clinical importance of these antibodies
has not been defined.
F. Miscellaneous Serum Tumor Markers
1 . Fibronectin
Fibronectin (FN) is a large glycoprotein that is a component
of the extracellular matrix and occurs in its soluble
form in plasma. A study of plasma FN concentrations in
dogs with malignancies documented both increased and
decreased plasma FN ( Feldman et al. , 1988 ). A study of
canine and feline pleural and abdominal effusions revealed
no useful distinction in FN concentrations between malignant
and nonmalignant effusions, although the FN/albumin
ratio was higher in dogs with malignant effusions compared
to those with congestive heart failure ( Hirschberger and
Pusch, 1996 ).
2 . Sialic Acid
Sialic acid describes derivatives of neuraminic acid, which
are potentially useful tumor markers because of the aberrant
glycosylation in cancer cell membranes. Although
the cancer specificity of sialic acid is reported to be high,
its sensitivity is low because sialic acid-rich glycoproteins
are present in inflammatory diseases ( Narayanan,
1994 ). Increased serum sialic acid concentration has been
observed in cancer-bearing dogs ( Poli et al. , 1986 ); however,
further studies suggest the increase is not specific for
cancer ( Thougaard et al. , 1998 ).
3 . Acute-Phase Proteins
The acute-phase proteins (APP) are those plasma proteins,
made primarily by hepatocytes, whose concentrations
change after tissue injury or infection. Their relationship
with cancer has long been recognized in human medicine
( Cooper and Stone, 1979 ). An increase in APP at the time of
diagnosis is a negative prognostic indicator in human cancer
patients, and increases may also occur with advancing disease
( Cooper, 1988 ). APP that may have use as tumor markers
include ceruloplasmin (Cp), complement components
C3 and C4, α 1-acid glycoprotein (AGP), α1-proteinase
inhibitor ( α1-antitrypsin), α1-antichymotrypsin, haptoglobin
(Hp), fibrinogen (Fbn), C-reactive protein (CRP), and
serum amyloid A (SAA). As an example, increased serum
CRP has been shown to be a poor prognostic indicator in
people with multiple myeloma, melanoma, lymphoma,
and ovarian, renal, pancreatic, and gastrointestinal tumors
( Mahmoud and Rivera, 2002 ). Because interleukin 6 (IL-6)
and tumor necrosis factor alpha (TNF- α ) induce synthesis
of CRP and potentially other APP, they are also receiving
attention as potential biomarkers and therapeutic targets.
APP have been studied in veterinary medicine. In a
recent study of APP in diseased dogs, significant increases
in Cp, Hp, and CRP were observed in dogs with cancer and
other inflammatory diseases, and decreases with treatment
were associated with more favorable outcomes ( Tecles
et al. , 2005 ). Increased serum concentrations of AGP
at diagnosis have been observed to decrease with cancer
treatment and onset of clinical remission in dogs with
lymphoma, suggesting its potential as a biomarker ( Hahn
et al. , 1999 ).
III. FLOW CYTOMETRY
A. DNA Ploidy
The flow cytometer is frequently employed to determine
the DNA content of cancer cells in various veterinary
tumors ( Culmsee and Nolte, 2002 ). Most normal tissues,
reactive tissues, and benign tumors have diploid (2N)
DNA values. The different DNA content of tumor cells
compared to normal tissues may be the result of abnormal
DNA (aneuploidy) or due to increased DNA content with
cell division. Although aneuploidy has been identified in
a wide variety of veterinary tumors, it has not been studied
carefully as a prognostic indicator. Aneuploidy may predict
aggressive tumor behavior in canine hemangiopericytoma
( Kang et al. , 2006 ), canine mammary tumors ( Hellmen
et al. , 1993 ), canine melanoma ( Bolon et al. , 1990 ), and
possibly canine mast cell tumors ( Ayl et al. , 1992 ).
However, aneuploidy does not seem to predict biological
behavior or prognosis in equine melanomas ( Roels et al. ,
2000a ) or canine lymphomas ( Teske et al. , 1993 ).