Page 723 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 33 Hematopoietic Tumors 701

Proteomics and Serum Biomarkers
Proteomics comprises, simplistically, methodologies that ana-
lyze the entire protein component or protein signature of cells
VetBooks.ir (the proteome). Protein components of a cell (normal or malig-
nant) change over time with upregulation and downregulation
of gene expression in response to varied stimuli (e.g., growth
factors, environmental cues). It may therefore be possible to use
the field of proteomics to identify serum biomarkers of malig-
nancy (i.e., cancer-specific protein markers) and to further ana-
lyze response to therapy or even to predict which therapies are
appropriate for an individual patient’s tumor. Although in its
infancy in veterinary oncology, preliminary investigations of the
proteome of dogs with lymphoma have been reported 198–201 ;
however, they have yet to reach the level of sophistication in
which useful output would have a significant effect on clinical
decision making.
Several analytes in serum have been explored as biomark-
ers of lymphoma in the dog and have been reviewed. 202 These
include tumor and metabolic products, cytokines, cellular leak- • Fig. 33.9 Lateral radiographic projection of a dog with sternal and hylar
age enzymes, and serum proteins. Examples include thymi- lymphadenopathy due to lymphoma.
dine kinase 1, C-reactive protein, alpha-fetoprotein, alpha-1
glycoprotein levels, zinc, chromium, iron, endostatin, vascu-
lar endothelial growth factor (VEGF), lactate dehydrogenase, lymphocytosis, circulating atypical lymphocytes, or other periph-
haptoglobin, and antioxidants/oxidative stress markers. 203–214 eral cytopenias. In one study of 53 dogs with lymphoma, 28%
Although some have been grouped and commercialized (e.g., had circulating malignant cells and were considered leukemic,
TK Canine Cancer Panel [VDI Labs, Simi Valley, CA, USA], whereas bone marrow examination indicated involvement in
Canine Lymphoma Blood Test [cLBT; Avacta Animal Health, 57% of the dogs. 216 The presence of a few prolymphocytes and
Whetherby, UK]), the clinical, biologic, and prognostic signif- large lymphocytes with nucleoli in the circulation of dogs with
icance of these assays has yet to be definitively characterized. lymphoma may indicate bone marrow involvement. It is impor-
Intuitively, use of biomarkers to detect early relapse would have tant to remember these cells also can be seen with immune-
clinical utility if meaningful therapeutic decisions and options mediated and inflammatory/infectious diseases. As discussed
were identified that would result in enhancement of quantity previously, tumor cells within the peripheral and bone mar-
and quality of life. Currently, the lead-time provided over stan- row compartments can also be identified using clonality assays
dard clinical diagnosis of relapse is relatively short, limiting their (PARR) that are more sensitive than routine microscopic exami-
routine utility; definitive studies to support their application in nation in detecting malignant cells; however, the prognostic sig-
larger and more varied general populations of dogs with lym- nificance of the knowledge gained with more sensitive staging
phoma are currently lacking. methodologies has yet to be determined. 216–218 Although bone
marrow evaluation may offer prognostically valuable informa-
Clinical Staging tion, it is not necessary to perform the procedure if the client is
committed to treat regardless of stage.
After a diagnosis has been established, the extent of disease should
be determined and categorized by clinical staging. The WHO Imaging
staging system routinely used to stage dogs with lymphoma is pre- Evaluation of thoracic and abdominal radiographs may be
sented in Box 33.2. Most dogs (>80%) are presented in advanced important in determining the extent of internal involvement
stages (III–IV). Diagnostic imaging and assessment of bone mar- (Fig. 33.9). 121,219 Approximately 60% to 75% of dogs with multi-
row involvement may be indicated for staging. The degree to centric lymphoma have abnormalities on thoracic radiographs, with
which thorough staging is implemented depends on whether the one-third having evidence of pulmonary infiltrates (see Fig. 33.4)
result will alter the treatment plan, whether relevant prognostic and two-thirds having thoracic lymphadenopathy (sternal and
information is gleaned, and whether the clients need to know the tracheobronchial LNs [see Fig. 33.9]) and widening of the cranial
stage before initiating (or declining) a treatment plan. In addition, mediastinum (see Fig. 33.2). 121,122 Pulmonary infiltrates usually are
when comparing different treatment protocols with respect to effi- represented by an interstitial and/or alveolar pattern; however, nod-
cacy, consistent and similar staging diagnostics should be used to ules (rarely) and bronchial infiltrates can also occur. 220 Pleural effu-
avoid so-called “stage migration,” which results when one staging sion may also be present. Cranial mediastinal lymphadenopathy is
methodology is more accurate than another. 215 The effect of stage detected in 20% of dogs with lymphoma. 122,220 Abdominal radio-
migration on prognosis should be considered when comparing graphs reveal evidence of involvement of medial iliac (sublumbar)
different published outcomes. and/or mesenteric LNs, spleen, or liver in approximately 50% of
cases. In the authors’ practice, for the typical cases of canine mul-
Bone Marrow Evaluation ticentric lymphoma, imaging is limited to thoracic radiographs as
A bone marrow aspirate or core biopsy (from the proximal there is no prognostic difference between dogs with stage III and
humerus or iliac crest) is recommended for complete staging IV disease (i.e., liver/spleen involvement); however, cranial medi-
and prognostication and may be indicated in dogs with anemia, astinal lymphadenopathy is of prognostic significance. If there are