Comparison of mitotic index and Ki67 index in the prognostication of canine cutaneous mast cell tumours.

Proliferation markers are commonly used for prognostication of mast cell tumours. The aim of the study is to compare the relative abilities of Ki67 and mitotic index to predict survival in the same cohort of dogs with cutaneous MCTs. Histological grade, mitotic index and Ki67 index were performed in all samples and clinical information was obtained by a follow-up questionnaire. Ninety-five dogs were included in the study with a median follow-up of 1145 days. Survival times varied significantly between categories of histological grade, mitotic index and Ki67 index. Multivariable analyses showed that the risk of dying due to MCT was similar in dogs with increased Ki67 index [hazard ratio, HR: 3.0 (95% CI 1.3-6.8)] or increased mitotic index [HR: 2.7 (95% CI 1.1-6.5)]. In conclusion, both mitotic index and Ki67 index were able to independently differentiate MCTs with worse prognosis. This distinction is particularly meaningful in selecting intermediate grade MCTs that may benefit from more aggressive local or systemic treatment.

Immunosuppression facilitates the reactivation of latent papillomavirus infections.

At mucosal sites, papillomavirus genomes can persist in the epithelial basal layer following immune-mediated regression. Subsequent T-cell depletion stimulates a 3- to 5-log increase in the viral copy number, to levels associated with productive infection. Reappearance of microlesions was rare within the short time frame of our experiments but was observed in one instance. Our studies provide direct evidence that immunosuppression can trigger the reactivation of latent papillomavirus genomes, as previously proposed in humans.

Rectal lymphoma in 11 dogs: a retrospective study.

OBJECTIVES: To retrospectively evaluate the clinical behaviour and immunophenotype of lymphoma of the rectum in dogs. METHODS: Eleven dogs diagnosed with lymphoma of the rectum on histopathology were retrospectively reviewed. Immunohistochemistry with CD3 and CD79a antibodies was performed at diagnosis or retrospectively. RESULTS: Treatment protocol varied with six dogs undergoing surgery and adjuvant chemotherapy, two received chemotherapy after only incisional biopsy, one had surgical resection only, one was treated symptomatically and one dog was not treated. Chemotherapy treatment consisted of either a -low-dose COP (cyclophosphamide - prednisolone - vincristine) protocol (four dogs) or a six-week CHOP-based (cyclophosphamide - vincristine - -prednisolone - anthracycline) protocol (four dogs). Dogs that received chemotherapy lived significantly longer than dogs that did not receive chemotherapy (2352 versus 70 days). Median survival time was not reached, and there was an overall mean survival time of 1697 days. Immunohistochemistry was performed in 10 of 11 samples, and was consistent with B-cell -lymphoma in all cases. CLINICAL SIGNIFICANCE: Canine lymphoma of the rectum is associated with a favourable prognosis. Immunohistochemical evaluation of these lesions was consistent with B-cell lymphoma in all cases in which it was examined.

Evaluation of minichromosome maintenance protein 7 as a prognostic marker in canine cutaneous mast cell tumours.

Minichromosome maintenance proteins (MCMs) are sensitive markers of cellular proliferation and have been shown to be significant predictors of survival in several human malignancies. MCM7 was evaluated as a prognostic marker in canine cutaneous mast cell tumours (MCTs). MCM7 immunohistochemistry was performed and an index of MCM7-positive cells calculated in dogs with known outcome. The Receiver Operating Characteristics method was used to individuate the best cut-off value of MCM7 score as predictor of survival. Survival analysis and prognostic variables were analysed with statistical methods. Ninety-five dogs were included with 31 dying of MCTs. A value of 0.18 was used as cut-off value of MCM7 score as a binary variable. The median survival time for MCM7 score ≤0.18 was not reached at 3668 days, whereas for MCM7 score >0.18 was 187 days (log-rank test; P < 0.0001). In the multivariable analysis, MCM7 was significantly associated with survival after controlling for age, surgical margins and histological grade (hazard ratio 9.2; P = 0.001).

Association of Ki67 index with prognosis for intermediate-grade canine cutaneous mast cell tumours.

Intermediate-grade mast cell tumours (MCT) represent a heterogeneous population of tumours. The prognosis for the majority of dogs is excellent following surgical excision, but a minority die because of their disease. A previous study identified Ki67 expression as a predictor of prognosis in all three grades of MCT. The purpose of this study was to validate those results in a new group of dogs, with intermediate-grade MCT only. Ki67 immunohistochemistry was performed on intermediate-grade MCT from 163 dogs with known outcome. Digital microscopy images were taken from each tumour, and an index calculated of Ki67-positive cells. Ki67 index as a binary variable with a cut-off value of 1.8% was confirmed to be associated with prognosis (hazard ratio = 19.1, P < 0.0001) for this cohort of dogs. The 1-year, 2-year and 3-year survival probabilities (with standard errors) of 127 dogs with a Ki67 index 1.8% were 0.54 (0.100), 0.45 (0.101) and 0.33 (0.104), respectively.

Vinblastine and prednisolone chemotherapy for surgically excised grade III canine cutaneous mast cell tumours.

The effect of treatment with vinblastine and prednisolone chemotherapy in dogs undergoing only surgical excision of Patnaik grade III cutaneous mast cell tumours is reported. Potential explanatory variables were explored using Kaplan-Meier survival analysis with log-rank tests. During a median follow-up period of 429 days, the overall median survival time (MST) was not reached (lower 95% CI = 322 days). The 1-year survival probability was 0.71 (standard error 0.1), remaining unchanged at 2 years. Secondary disease at presentation was an independent risk factor for survival (P = 0.045). The MST of dogs presenting with secondary disease was 322 days, with a lower 95% confidence interval of 142 days and a 1-year survival of probability of 0.47 (standard error 0.19). Adverse effects were recorded in 6 of the 108 (5.6%) vinblastine doses given. This chemotherapy regimen is a well-tolerated adjunct to surgery for grade III mast cell tumours and appears to prolong survival compared with that expected with surgery alone.

Role of carboplatin in multi-modality treatment of canine tonsillar squamous cell carcinoma--a case series of five dogs.

Canine tonsillar squamous cell carcinoma is an aggressive disease with a poor prognosis. A retrospective study was undertaken of all dogs that were presented between January 1999 and January 2004 to the Animal Health Trust for the treatment of tonsillar squamous cell carcinoma. Five cases were identified, and their median survival time was 211 days (95 per cent confidence interval 80 to 352) with two of the five dogs remaining alive at the end of the study, 826 and 1628 days from diagnosis with no clinical signs of disease. The protocol was well tolerated with only one of the five dogs showing toxicity associated with carboplatin and all dogs that started radiotherapy completing it. Compared with results of previous studies, these cases suggest that surgical cytoreduction followed by coarse fractionated radiotherapy together with carboplatin may be a useful way to treat this tumour. Carboplatin alone caused partial remission in the two cases where it was used as neo-adjunctive therapy.

Oral malignant melanoma - the effect of coarse fractionation radiotherapy alone or with adjuvant carboplatin therapy.

Abstract A retrospective study was undertaken of dogs presented to the Animal Health Trust for treatment of oral malignant melanoma, without radiographic evidence of pulmonary metastases. Group 1 (n = 13) received radiotherapy of the primary and any lymph node metastases (4 weekly fractions of 9 Gy); and group 2 (n = 15) were treated the same but additionally received between two and six doses carboplatin at 300 mg m(-2) every 3 weeks. Median survival times for the two groups were 307 and 286 days, respectively (P > 0.05). In addition, carboplatin therapy did not significantly reduce the proportion of dogs dying due to metastases (three from group 1 and four from group 2). We found no evidence of a beneficial effect of carboplatin therapy over radiotherapy alone.