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

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Chapter | 25 Tumor Markers
when compared to dogs with noninflammatory malignant
mammary tumors ( Illera et al. , 2006 ).
The presence of progesterone receptors has been
described in lymphomas of the horse ( Henson et al. , 2000 ).
A case report describing the regression of a cutaneous
lymphoma in a mare after removal of GTCT hints at the
biological significance of progesterone receptors in equine
lymphomas ( Henson et al. , 1998 ).
7 . Insulin
Increased secretion of insulin from the beta cells of the
pancreas is the hallmark of insulinoma (beta cell tumor,
pancreatic islet cell tumor). Although several variations on
the insulin-glucose ratio appear in the literature, documentation
of the abnormal physiological condition of fasting hypoglycemia
and measurable serum insulin is sufficient for the
diagnosis of insulinoma. Measuring serum fructosamine and
glycated hemoglobin may also be helpful in the diagnosis of
insulinoma. In a few small series of dogs with insulinoma,
decreased serum fructosamine concentrations ( Loste et al. ,
2001 ; Mellanby and Herrtage, 2002 ) and decreased serum
glycated hemoglobin concentrations ( Elliott et al. , 1997 ;
Marca et al. , 2000 ) have been observed. Low serum fructosamine
may indicate the presence of insulinoma despite normoglycemia
( Mellanby and Herrtage, 2002 ).
C. Enzymes
1. Lactate Dehydrogenase, Serum Alkaline Phosphatase,
Prostatic Acid Phosphatase, Thymidine Kinase
Lactate dehydrogenase (LDH), an enzyme that cata lyzes
the interconversion of pyruvate and lactate, has been studied
in humans with a variety of malignancies, but it is best
validated as a marker for evaluating prognosis in patients
with nonseminomatous germ cell tumors ( Duffy, 2004 ).
LDH activity, along with activity of several of its isoenzymes,
is increased in dogs with lymphoma; dogs with
lower serum LDH activity had overall longer survival
times compared to dogs with increased LDH activity, suggesting
this may be a useful marker for canine lymphoma
( Zanatta et al. , 2003 ). Increased plasma and urine LDH
activity have been observed in cows with urinary bladder
cancer ( Dawra et al. , 1991 ).
Elevated serum alkaline phosphatase (ALP) activity is
a prognostic factor in humans with a variety of advanced
cancers ( Hauser et al. , 2006 ) and may predict outcome in
a variety of cancers including prostate cancer ( Cho et al. ,
2003 ) and advanced uveal melanoma ( Eskelin et al. , 2003 ).
Serum ALP activity has apparently no value as a tumor
marker for canine lymphoma or canine mammary tumors
( Karayannopoulou et al. , 2003 ; Wiedemann et al. , 2005 ).
Pretreatment elevated serum ALP activity and failure to
return to normal ALP activity after treatment correlate
with poor survival of dogs with appendicular osteosarcoma
( Ehrhart et al. , 1998 ; Garzotto et al. , 2000 ).
Prostatic acid phosphatase (PAP), a neutral protein
tyrosine phosphatase, was widely used as a tumor marker
before the discovery of prostate-specific antigen. Serum
PAP activity is increased in men with prostate cancer and
has important cellular functions in carcinogenesis of the
prostate ( Veeramani et al. , 2005 ). However, this increase
does not appear to occur in dogs with prostate cancer ( Bell
et al. , 1995 ).
Thymidine kinase (TK), a phosphotransferase enzyme
found in most living cells, has been evaluated as a tumor
marker in women with breast cancer, showing a decrease in
serum activity after surgical treatment of the primary tumor
(He et al. , 2000 ). It may also provide prognostic information
in humans with non-Hodgkin’s lymphoma and multiple
myeloma ( Diem et al. , 1993 ; Hallek et al. , 1992 ). In dogs
with lymphoma, serum TK activity appears to be a predictor
of survival ( von Euler et al. , 2004 ). TK can now be measured
with nonradiometric methods, making it more appealing
for routine laboratory use ( von Euler et al. , 2006 ).
D. Immunoglobulins
A long-standing use of a serum tumor marker in veterinary
medicine is the measurement of serum immunoglobulins.
In diseases of B cells, including multiple myeloma and
Waldenström’s macroglobulinemia, hyperglobulinemia is
often present. Electrophoresis of the serum proteins reveals
a typical monoclonal gammopathy, and immunoelectrophoresis
is used to further characterize the antibody class of the
immunoglobulins. The hyperglobulinemia resolves with
successful treatment and therefore makes a convenient measure
to assess response and recurrence. IgM, IgG, and IgA
gammopathies have been described in the dog ( Giraudel
et al. , 2002 ; Lautzenhiser et al. , 2003 ; Ramaiah et al. , 2002 ).
It should be noted that hypergammaglobulinemia does not
occur with all cases of myeloma, and there may be hypogammaglobulinemia
with a normal electrophoretic pattern.
Canine ehrlichiosis infection can also cause a monoclonal
gammopathy and should be considered among the differential
diagnoses for increased serum immunoglobulins
(Breitschwerdt et al. , 1987 ).
E. Tumor-Associated Antigens
1 . CA-125
Cancer antigen 125 (CA-125) is a product of the MUC16
gene and has found use in human medicine as a tumor
marker for epithelial ovarian cancers, although the sensitivity
and specificity are poor ( Moss et al. , 2005 ). Serum CA-125
may be elevated in other cancers, such as endometrial cancer,
cancer of the fallopian tubes, lung cancer, breast cancer, and