Canine mast cell tumors: correlation of apoptosis and proliferation markers with prognosis.
The Patnaik histologic grading system is commonly used to predict the behavior of cutaneous mast cell tumors (MCTs) in dogs, but it is less useful for grade 2 MCTs because they exhibit considerable variation in biological behavior. In this retrospective study, immunohistochemical staining for Ki-67, proliferating cell nuclear antigen (PCNA), and survivin and a standardized argyrophilic staining of nucleolar organizer regions (AgNOR) protocol were performed on 121 archived paraffin-embedded specimens of canine cutaneous MCTs, for which clinical follow-up data were available. Cox regression models indicated that the Ki-67 score (hazard ratio, 1.92; P < .001) and mean AgNOR score (hazard ratio, 2.57; P < .001) were significantly associated with Patnaik grade and survival time. A binary Ki-67 variable (cutoff point Ki-67 score = 1.8) was a significant predictor of survival for dogs with grade 2 MCTs. The estimated 1-, 2-, and 3-year survival probabilities for dogs with grade 2 MCTs and Ki-67 scores less than 1.8 were 0.92, 0.86, and 0.77, respectively (SEs, 0.08, 0.14, and 0.23, respectively; median not estimable). The corresponding survival probabilities for dogs with grade 2 MCTs and Ki-67 scores higher than 1.8 were 0.43, 0.21, and 0.21, respectively (SEs, 0.19, 0.18, and 0.18, respectively; median survival time, 395 days). No significant association was identified between survival and survivin score or PCNA score. This study shows that both mean AgNOR score and Ki-67 score are prognostic markers for canine MCTs. The Ki-67 score can be used to divide Patnaik grade 2 MCTs into 2 groups with markedly different expected survival times.
Oncology Research Group, Animal Health Trust, Lanwades Park, Kentford, Newmarket, United Kingdom. tim.scase@aht.org.uk
Timothy J
TJ
Scase
David
D
Edwards
Jodi
J
Miller
William
W
Henley
Ken
K
Smith
Anthony
A
Blunden
Sue
S
Murphy
D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D015415:Biomarkers; D049109:Cell Proliferation; D004283:Dog Diseases / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D012515:Mast-Cell Sarcoma / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism
D034961:Antigens, Nuclear; D015415:Biomarkers; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; C051963:nucleolar organizer region associated proteins