Mastocitomas caninos diagnosticados na região central do Rio Grande do Sul: graduação histológica, padrão de expressão da proteína KIT e investigação de mutações

Abstract

Mast cell tumor (MCT) is a malignant neoplasm originating from mast cells that can arise in different tissues. Its biological behavior is highly variable, especially when it originates in the skin, which has stimulated several studies about prognostic factors. In addition to the histological grading system proposed by Kiupel (2011), the Ki67 index, the immunostaining pattern for KIT and c-kit mutation status for exons 8 and 11 are some of the most recently mentioned prognostic tools. The prevalence of mutations in c-kit exons 8 and 11, when added together, were observed in up to 45% of cases in canine cutaneous mast cell tumors. The main objective of this study was to characterize the anatomopathological and molecular aspects of mast cell tumors in biopsies and mast cell tumors in necropsies of dogs from the diagnostic routine of the Laboratory of Veterinary Pathology (LPV) of the Federal University of Santa Maria (UFSM). With this information, two scientific articles were prepared. The first article characterized 16 dogs with metastatic MCTs submitted to necropsy between 2012-2022. Mast cell tumors were evaluated histologically and submitted to Toluidine Blue (TB) staining, immunohistochemistry (IHC) for KIT and Polymerase Chain Reaction (PCR) for exons 8 and 11. The primary locations observed were skin and/or subcutaneous tissue (13), intestine (2), and periocular tissue (1). Five dogs resected the neoplasm before systemic dissemination and six had undergone chemotherapy. Metastases were most common in local lymph nodes (16), liver (16) and spleen (15). Histologically, mast cell tumors ranged from well differentiated, with abundant granules, to poorly differentiated, with scarce granules. The KIT pattern of all cases was aberrant, in 9 cases were pattern II and 7 cases were pattern III. The primary and metastatic site pattern was identical. Exons 8 and 11 were amplified in seven neoplasms from four dogs, with no mutation detected. It is hoped that this study will help veterinary oncologists in the diagnosis, prognosis and therapy of MCTs with a more aggressive biological behavior. The second article aimed to investigate the presence of mutations in exons 8 and 11 of c-kit in 45 canines cutaneous MCTs diagnosed in southern Brazil. All MCTs were evaluated histologically with the methods of Patnaik and Kiupel, submitted to IHC for KIT and PCR in search of mutations in exons 8 and 11. Twenty-five tumors were classified as low grade, and 20 as high grade. As for the KIT expression patterns, pattern I (12), II (29) and III (2), in addition to two tumors that did not show immunolabelled cells. Thirteen cases were positive for exon 11 mutations, the majority being from frozen samples. Amplification of the DNA region for exon 8 occurred in only thirteen cases and all were mutation negative. This study was important in characterizing the immunohistochemical and molecular aspects of cutaneous mast cell tumors diagnosed in southern Brazil.