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Objective-To evaluate recurrence rate and disease-free interval (DFI) of dogs with low-grade soft tissue spindle cell sarcoma of the extremities treated by marginal excision. Study Design-Retrospective study. Animals-Dogs (n ¼ 35) with soft tissue low-grade spindle cell sarcoma. Methods-Medical records were reviewed and dogs that had marginal surgical resection of lowgrade soft tissue spindle cell sarcoma at or distal to elbow and stifle were included. Results-Histopathologic margins were dirty (12 dogs), clean but close (12), and clean (11). Followup after surgery occurred from 210 to 2202 days (minimum, 180 days). Local recurrence and metastatic rates were 10.8% and 0%, respectively. Median DFI and survival time were not reached, because o50% of dogs died of disease-related events. Mean DFI and mean survival time were 697.8 days (95% CI: 559.7-836 days) and 703.5 days (95% CI: 566.6-840.5 days), respectively. There were no significant differences among survival functions stratified by histologic margins. Conclusion-Marginal surgical excision without adjuvant treatment of low-grade soft tissue spindle cell sarcoma of the extremities results in a low local recurrence rate. Clinical Relevance-Low-grade spindle cell sarcomas located at or distal to the elbow and stifle joints can be excised without need for wide or radical surgery. r

The expression of Ki67, BCL-2, and COX-2 was investigated in 53 canine cutaneous mast cell tumors (MCTs) by immunohistochemistry and quantitative real time polymerase chain reaction (qPCR) to evaluate their prognostic significance and the association with the histologic grading and the mitotic index (MI). MCTs were graded according to the Patnaik grading system and the novel 2-tier grading system proposed by Kiupel. The numbers of mitotic figures/10 high-power fields (MI) were counted. Both grading systems were significantly associated with prognosis. The Patnaik grading was of limited prognostic value for grade 2 MCTs, with 23% being associated with mortality. The concordance among pathologists was strongly improved by the application of the 2-tier grading system, and 71% of high-grade MCTs were associated with a high mortality rate. MI and Ki67 protein expression were significantly associated with grading and survival. No significant association between BCL-2 protein expression and either grading system or health status was observed. BCL-2 mRNA expression was significantly higher in grade 2 than in grade 1 MCTs, while no statistically significant differences were detected between low- and high-grade MCTs. The increased BCL-2 mRNA level was significantly associated with increased mortality rate. The COX-2 protein expression was detected in 78% of the MCTs investigated. However, neither association with the tumor grade nor with the health status was observed. COX-2 mRNA was significantly up-regulated in MCTs compared to surgical margins and control skin tissue, but it was neither associated with tumor grade nor with survival.

Lymph node (LN) metastasis in canine cutaneous mast cell tumours (cMCTs) is a well-known negative prognostic factor. The role of lymphadenectomy in the treatment of stage II disease remains controversial because of its uncertain therapeutic benefit. Aim of this retrospective study was to investigate the impact of lymphadenectomy on tumour control and survival for dogs with stage II cMCTs. Dogs with firstly occurring, histologically confirmed cMCT with LN metastasis undergoing resection of the primary tumour and medical treatment thereafter were retrospectively enrolled. Dogs were classified into two groups: LN sampling (LNS; diagnosis of metastasis obtained by cytology) and regional LN dissection (LND; diagnosis obtained by histopathology). To determine the therapeutic value of lymphadenectomy, the characteristics of recurrence (local, nodal and distant) and survival were compared between groups. Evaluated outcome variables included signalment, anatomic location, diameter, ulceration, substage, surgical margins, Patnaik grading, Kiupel grading and medical treatment. Overall, 152 dogs were included: 81 underwent LND as part of primary surgery and 71 LNS. The median follow-up time was 409 days for LND group and 620 days for LNS group. On univariable analysis, the risk of developing local, nodal or distant relapse was significantly higher in the LNS group compared with LND (P < 0.001). On multivariable analysis, the risk of tumour progression and tumour-related death were 5.47 and 3.61 times higher in the LNS group, respectively (P < 0.001). Regional lymphadenectomy may have therapeutic value and improve prognosis in dogs with stage II cMCTs undergoing surgical removal of the primary tumour and medical treatment.

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Purpose: Due to the many similarities with its human counterpart, canine malignant melanoma (cMM) is a valuable model in which to assess the efficacy of novel therapeutic strategies. The model is herein used to evaluate the immunogenicity, safety, and therapeutic efficacy of a human chondroitin sulfate proteoglycan-4 (hCSPG4) DNA-based vaccine. The fact that homology between hCSPG4 and cCSPG4 amino-acidic sequences stands at more than 80% provides the rationale for using an hCSPG4 DNA vaccine in the cMM model.Experimental Design: Dogs with stage II-III surgically resected CSPG4-positive oral MM were subjected to monthly intramuscular plasmid administration, which was followed immediately by electroporation (electrovaccination) for at least 6, and up to 20, months. The immunogenicity, safety, and therapeutic efficacy of the vaccine have been evaluated.Results: hCSPG4 electrovaccination caused no clinically relevant local or systemic side effects and resulted in significantly longer overall and disease-free survival times in 14 vaccinated dogs as compared with 13 nonvaccinated controls. All vaccinated dogs developed antibodies against both hCSPG4 and cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T-cell response and only two gave a detectable interferon (IFN)g response.Conclusion: Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the "self" antigen and seems to be effective in treating cMM, laying the foundation for its translation to a human clinical setting.

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