Evaluation of the Proliferative Activity of Diffuse Large B-Cell Lymphoma (DLBCL) in Dogs with Respect to Patient Eligibility for Anthracycline-Based Chemotherapy

SIMPLE SUMMARY: Canine lymphomas usually have aggressive behavior, but respond well to chemotherapy. Despite proper diagnosis and numerous available therapeutic regimens, it is difficult to determine the prognosis and choose the optimal method of treatment in each individual patient. Diffuse large B-cell lymphoma is the most commonly diagnosed histological subtype of canine lymphoma and is treated with anthracyclines alone or in combination with other chemotherapeutics. A new diagnostic marker of prognostic and predictive value is topoisomerase IIα, which also constitutes a molecular target for anti-cancer drugs belonging to the group of topoisomerase IIα inhibitors including anthracyclines. Proliferative activity was estimated in samples of enlarged lymph nodes in dogs with diffuse large B-cell lymphoma based on mitotic count and immunohistochemical evaluation of topoisomerase IIα and Ki67 antigen expression with a view to qualifying patients for anthracycline-base chemotherapy. It has been shown that higher levels of topoisomerase IIα expression corresponded to a higher mitotic count but not to Ki67 index. These results indicate that an immunohistochemical evaluation of topoisomerase IIα expression can be used to develop a diagnostic-clinical protocol for the treatment of dogs with diffuse large B-cell lymphoma using anthracycline-based chemotherapy. ABSTRACT: Different types of canine lymphoma respond differently to chemotherapy and have different prognoses. Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in dogs. Topoisomerase II alpha (TOPIIα) protein has been shown to be a proliferation marker associated with prognostic significance. The aim of the study was to determine the relationship between TOPIIα expression, mitotic count (MC), and Ki67 antigen index in DLBCL in dogs, taking into account the applicability of these parameters to select the chemotherapy protocol with emphasis on the use of anthracycline drugs. Samples of formalin-fixed paraffin-embedded lymph nodes from 34 dogs with DLBCL were immunohistochemically labelled with anti-TOPIIα and Ki67. The number of positive cells and the intensity of the reaction were taken into account in order to assess TOPIIα expression. MC was estimated in the hematoxylin and eosin-stained slides in the area of 2.37 mm(2). Positive association between TOPIIα and MC, but no association between TOPIIα and Ki67 was found. It can be concluded that the immunohistochemical determination of TOPIIα as a molecular target for drugs from the anthracycline group may be used in association with MC to establish a diagnostic-clinical protocol for selecting dogs with DLBCL for treatment with anthracycline drugs.