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

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Chapter | 25 Tumor Markers
be distinguished based on the observed immunoreactivity
to a cytokeratin panel ( Walter, 2000 ). Cytokeratin 6 is
present in all epithelial skin tumors with the exception of
pilomatrixoma. Cytokeratin 14 reactivity occurs in basal
cell-derived neoplasms and in sebaceous and perianal gland
tumors, whereas reactivity to cytokeratin 10/11 is limited
to spinous cell-derived tumors and cytokeratin 8/18 immunoreactivity
occurs only in tumors of sweat gland origin.
Cytokeratin immunostaining has also been used to detect
micrometastases in lymph nodes of dogs with mammary
gland carcinoma that were considered negative on routine
evaluation of H & E stained specimens ( Matos et al. , 2006 ).
B. Mesenchyme
1 . Vimentin
Vimentin intermediate filaments are used to mark nonmuscle
sarcomas ( Fox et al. , 2002 ; Mazzei et al. , 2002 ).
Vimentin expression is lost during the process of differentiation
of skeletal muscle and is absent in normal mature
myofibrils. Vimentin intermediate filaments have been
reported, however, in poorly differentiated rhabdomyosarcomas
( Brockus and Myers, 2004 ).
2 . Desmin
Desmin is the cytoskeletal component that holds myofibrils
in place, and it has found use as a marker for canine leiomyomas
and leiomyosarcomas ( Sato et al. , 2003 ). Canine
skeletal muscle tumors are also reactive to desmin antibodies
( Illanes, 2002 ). Canine hemangiopericytoma may also
express desmin ( Mazzei et al. , 2002 ).
3 . Fibrillary Acid Protein
Glial fibrillary acid protein (GFAP) is found in glial
cells in the central nervous system, in Schwann cells and
schwannomas, and other tissues. In dogs, GFAP reactivity
occurs in glial cells, including fibrous astrocytes, Schwann
cells, axons, and cell bodies of peripheral ganglia. It has
also been identified in glioblastoma multiforme of dogs
( Lipsitz et al. , 2003 ).
C. Drug Resistance
An important mechanism for cellular resistance to anticancer
drugs involves the overexpression of the product of the
MDR-1 gene, P-glycoprotein (Pgp). Pgp is an ATP-dependent
transmembrane efflux pump that reduces the intracellular
concentration of a variety of chemotherapy drugs. The presence
of Pgp can be detected with immunohistochemistry,
and Pgp expression is associated with a poor clinical outcome
in dogs with lymphoma ( Lee et al. , 1996 ).
D. Proliferation
1 . Ki-67
The monoclonal antibody (MIB-1) directed against Ki-67 recognizes
a nonhistone nuclear protein expressed in proliferating
cells during G1-, S-, G2-, and M-phases of the cell cycle,
but it is not present in quiescent (G0) cells. Immunostaining
for the Ki-67 antigen offers an efficient method for estimating
the proliferative fraction of a tumor and correlates well
with other measures of proliferation. Ki-67 labeling index
may have prognostic significance in canine mammary gland
tumors ( De Matos et al. , 2006 ; Zuccari et al. , 2004 ), soft tissue
sarcomas ( Ettinger et al. , 2006 ), and melanoma ( Laprie
et al. , 2001 ; Millanta et al. , 2002 ). The Ki-67 labeling index
is of limited value in predicting outcome in canine lymphoma
(Phillips et al. , 2000 ). Low Ki-67 labeling of feline squamous
cell carcinoma was predictive of a poor response to radiation
therapy ( Melzer et al. , 2006 ).
2 . Proliferating Cell Nuclear Antigen
Cyclin, also known as proliferating cell nuclear antigen
(PCNA), is a nonhistone nuclear protein that is present
throughout the cell cycle in proliferating cells, reaching its
maximum during S phase. Use of PCNA to estimate tumor
proliferation rate has value in predicting response to treatment
in dogs undergoing radiation therapy for meningioma ( Theon
et al. , 2000 ). PCNA immunoreactivity does not correlate with
survival canine mast cell tumors ( Scase et al. , 2006 ), canine
or feline lymphoma ( Kiupel et al. , 1998 ; Phillips et al. , 2000 ;
Vail et al. , 1998 ), canine or feline melanoma ( Roels et al. ,
1999 ), or canine soft tissue sarcomas ( Ettinger et al. , 2006 ).
E. Leukocyte Markers
The study of immune system malignancies has been
advanced by the development of monoclonal antibodies with
specific reactivity to canine and feline leukocyte antigens.
At present, leukocyte antigens are defined by clusterdifferentiation
(CD) numbers assigned by international
workshops. Panels of antibodies against leukocyte antigens
are useful for classifying round cell malignancies
and may provide prognostic information ( Fernandez et al. ,
2005 ). Commonly used antibodies to identify various cell
types of origin include CD3 (T cells), CD79a (B cells),
CD18 (leukocytes), canine CD11d (macrophages and
T cells), factor VIII-related antigen (megakaryocytes), and
CD45RA (leukocytes). T cells can be further characterized
as T cell helpers (CD4 reactive) or cytotoxic T cells (CD8
reactive). Peripheral T cells (thymocytes) can be identified
by their reactivity to Thy-1. B cells can also be identified
with CD20 ( Jubala et al. , 2005 ). MCH-II may also be used
to identify antigen-presenting cells. Plasma cells may be
identified by their immunoreactivity to canine immunoglobulin
antibodies ( Day, 1995 ).