Immunohistochemical detection of proliferating cell nuclear antigen and Ki-67 in mast cell tumors from dogs.

OBJECTIVE: To determine whether immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and Ki-67 correlated with prognosis for dogs with cutaneous mast cell tumors (MCT). DESIGN: Case series. ANIMALS: 120 dogs with solitary cutaneous MCT that were excised. PROCEDURE: Information on signalment, history, and outcome was obtained by sending a questionnaire to referring veterinarians. Tumors were graded histologically, and immunohistochemical staining for Ki-67 and PCNA was performed. RESULTS: Survival rates 12, 18, and 24 months after surgery were significantly different among groups when dogs were grouped on the basis of histologic grade. Although mean number of PCNA-positive nuclei/1,000 tumor nuclei was significantly higher for dogs that died of MCT than for those that survived, there was great overlap in values. Mean number of Ki-67-positive nuclei/1,000 tumor nuclei was significantly higher for dogs that died of MCT than for those that survived, without any overlap in values between groups, and number of Ki-67-positive nuclei/1,000 tumor nuclei was significantly different among groups when tumors were grouped on the basis of histologic grades. For dogs with grade-II tumors, number of Ki-67-positive nuclei/1,000 tumor nuclei (< 93 vs > or = 93) was significantly associated with outcome (survived vs died). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that for dogs with solitary cutaneous MCT, determining number of Ki-67-positive nuclei may be useful in predicting prognosis, particularly for dogs with grade-II tumors.

Urinary DNA as an indicator of nephrotoxicity caused by endotoxin and gentamicin in mice.

Extracellular DNA is a non-specific marker of cell death. Urinary DNA, as an indicator of nephrotoxicity, was investigated in endotoxin/gentamicin-injected mice. In mice injected both with endotoxin (15 mg/kg) and gentamicin (80 mg/kg), urinary DNA concentration was markedly increased for several days; in contrast, there was at most a slight and transient excretion of DNA in mice receiving gentamicin or endotoxin alone. Plasma DNA concentrations increased for 24-48 h in endotoxin-injected mice, then decreased rapidly. Mice injected with gentamicin and endotoxin showed widespread and severe kidney lesions with tubular cell necrosis and intraluminal casts while mice receiving gentamicin or endotoxin alone showed at most few and mild lesions. In mice receiving lower doses of endotoxin (5-10 mg/kg) and 80 mg/kg gentamicin, urinary DNA peaked at 72-96 h, at a time when plasma DNA had returned to normal concentrations. Maximal urinary DNA concentrations depended upon endotoxin dose. In conclusion, urinary DNA is a marker of definite cell death occurring in the urinary tract and could represent a new indicator of nephrotoxicity in clinical and experimental situations.