ABSTRACT
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.
Subject(s)
Dog Diseases/mortality , Ki-67 Antigen/metabolism , Mastocytoma/veterinary , Neoplasm Staging/veterinary , Skin Neoplasms/veterinary , Animals , Biomarkers , Cohort Studies , Dog Diseases/metabolism , Dog Diseases/pathology , Dogs , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Male , Mastocytoma/metabolism , Mastocytoma/mortality , Mastocytoma/pathology , Mitotic Index , Prognosis , Skin Neoplasms/metabolism , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Survival Analysis , Time FactorsABSTRACT
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).
Subject(s)
Biomarkers, Tumor , Cell Cycle Proteins/metabolism , DNA-Binding Proteins/metabolism , Dog Diseases/metabolism , Mastocytoma, Skin/veterinary , Nuclear Proteins/metabolism , Animals , Cell Cycle Proteins/genetics , DNA-Binding Proteins/genetics , Dog Diseases/mortality , Dog Diseases/pathology , Dogs , Female , Gene Expression Regulation, Neoplastic , Male , Mastocytoma, Skin/metabolism , Mastocytoma, Skin/mortality , Nuclear Proteins/genetics , Prognosis , Retrospective StudiesABSTRACT
Eyes from 88 otters found dead in south-west England between 1990 and 2000, were collected as part of a larger pathological study. Histopathological examination of 131 eyes revealed dysplastic changes such as rosetting and folding in the retinas of 26 of the otters. In the eyes of 42 of the otters there were postmortem and fixation-induced retinal detachment which complicated the differentiation of dysplastic from normal retina, but 11 eyes had folds which probably indicated a dysplastic pathology. The eyes of 18 of the otters had inflammatory or autolytic changes which precluded a definitive evaluation of their dysplastic status. Liver samples from 55 of the otters were analysed for a range of polychlorinated hydrocarbons and for vitamin A. The otters with dysplastic retinas had significantly lower concentrations of vitamin A and higher concentrations of dieldrin than the otters with normal retinas.
