Systematic Review of Methods and Prognostic Value of Mitotic Activity. Part 2: Canine Tumors

Abstract

One of the most relevant prognostication tests for tumors is cellular proliferation, which is most commonly measured by the mitotic activity in routine tumor sections. The goal of this systematic review is to scholarly analyze the methods and prognostic relevance of histologically measuring mitotic activity in canine tumors. A total of 137 articles that correlated the mitotic activity in canine tumors with patient outcome were identified through a systematic (PubMed and Scopus) and manual (Google Scholar) literature search and eligibility screening process. These studies determined the mitotic count (MC, number of mitotic figures per tumor area) in 126 instances, presumably the mitotic count (method not specified) in 6 instances and the mitotic index (MI, proportion of mitotic figures per tumor cells) in 5 instances. A particularly high risk of bias was identified in the available details of the MC methods and statistical analysis, which often did not quantify the prognostic discriminative ability of the MC and only reported p-values. A significant association of the MC with survival was found in 72/109 (66%) studies. However, survival was evaluated by at least three studies in only 7 tumor types/groups, of which a prognostic relevance is apparent for mast cell tumors of the skin, cutaneous melanoma and soft tissue sarcoma of the skin. None of the studies on the MI found a prognostic relevance. Further studies on the MC and MI with standardized methods are needed to prove the prognostic benefit of this test for further tumor types.