Page 536 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

514 PART IV Specific Malignancies in the Small Animal Patient

but are not limited to, microsatellite instability, EGFR mutations, requires biopsy and histopathology. Characteristic histopathology
P53 inactivation, Rb inactivation, P16INK4a inactivation, allelic often demonstrates angiocentric and angiodestructive infiltra-
tion of the pulmonary parenchyma by large lymphoreticular and
loss, and high telomerase activity. K-ras mutations have been
VetBooks.ir found in up to 30% of human NSCLC. 377 Close homology exists plasmacytoid cells in addition to normal appearing lymphocytes,
eosinophils, and plasma cells. This infiltrate is typically centered
between canine and human K-ras. Interestingly, K-ras mutations
were detected in five of 21 canine NSCLC specimens by direct around small to medium arteries and veins.
sequencing. 262 Further studies concluded that the frequency and The etiology of this disease is unknown but is suspected to
type of mutations in canine NSCLC tissues more matched those be neoplastic or preneoplastic. Clonality has been identified on
for tumors from human nonsmokers with K-ras mutations than PARR, but this finding needs to be investigated in a larger series
those for smokers. 262 of cases. 385 Additional molecular diagnostics, such as immunohis-
Recent developments in biomarker driven targeted therapies tochemistry in combination with clonality testing, may eventually
of lung tumors have improved survival rates for NSCLC patients, result in a better understanding of this disease. 386 It is not known
including those with EGFR mutations or anaplastic lymphoma whether flow cytometry or PARR testing may possibly improve
kinase (ALK) rearrangements. The FDA has approved the use of the diagnostic power of fine-needle aspirates.
several TKIs based on large prospective trials, and these drugs are In a very limited number of cases, the response to chemo-
considered part of first-line standard-of-care in certain molecu- therapy has been quite variable. 387 Of five dogs that were treated
larly defined subsets of patients with advanced NSCLC. Unfortu- with cyclophosphamide, vincristine, and prednisone, three dogs
nately, this pertains to only a minority of patients with NSCLC, achieved a complete response. The remaining two dogs either
and acquired resistance to such therapies is commonplace. EGFR showed worsening clinical signs or progressed to lymphoid leu-
expression has recently been associated with anthracosis and a kemia within months. Dogs achieving a complete response were
trend toward shortened STs in dogs with primary lung tumors; alive at 7, 12, and 32 months.
however, mutational status of canine primary lung tumors has
not been extensively performed. 270 An increased expression of References
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