Search

Objective: To examine effects of a common mutation (2-base insertion in exon 5) of the TP53 gene on biological function of p53 protein in canine histiocytic sarcoma cells., Sample: Canine histiocytic tumor cell lines DH82 with deletion of TP53 and CHS-3 with the wild-type TP53 and canine wild-type and mutant TP53 fragments., Procedures: Wild-type or mutant TP53 with a polyprotein peptide tag at the N-terminus was transduced into DH82 and CHS-3 cells. Expression of p53 protein, changes in function as a transcription factor, and susceptibility to doxorubicin and nimustine were compared., Results: Transduced p53 protein was detected in wild-type TP53 -transduced DH82 and CHS-3 cells, whereas expression was not detected in mutant TP53 -transduced cells. There were significant increases in expression of target genes of p53 protein, including p21 and MDM2 , in wild-type TP53 -transduced cells, compared with results for native and mock-transfected cells, but not in mutant TP53 -transduced cells. There was no significant difference in drug susceptibilities among native and derivative cells of CHS-3. However, cell viabilities of wild-type TP53 -transduced DH82 cells incubated with doxorubicin were significantly lower than viabilities of native, mock-transfected, and AT insertion mutation- TP53 -transduced DH82 cells; susceptibility to nimustine did not differ significantly among cells., Conclusions and Clinical Relevance: Expression of p53 protein and its function as a transcription factor were lost after addition of a 2-base insertion in the TP53 gene in canine histiocytic tumor cells. Additional studies are needed to investigate the clinical relevance of this mutation in histiocytic sarcomas of dogs.

A 7-year-old female domestic rabbit suffered from labored respiration, poor appetite, mild anemia and thrombocytopenia. Radioscopic examination revealed masses in multiple locations including the intrapleural cavity and spleen. Forty-three days after the first visit to a private veterinary clinic, the rabbit died of severe respiratory distress. Microscopically, all of the masses were composed of round to polygonal neoplastic cells with distinct cell borders that were arranged in a sheet pattern. Multinucleated giant neoplastic cells were often observed. Some neoplastic cells had phagocytozed one or more erythrocytes. Immunohistochemical staining revealed that the neoplastic cells expressed vimentin, CD204, Iba-1 and lysozyme, but not CD163. Based on the morphological and immunohistochemical findings, this case was diagnosed as disseminated histiocytic sarcoma with hemophagocytosis.

Histiocytic sarcoma is a rapidly progressive and fatal neoplastic disease in dogs. It is unclear whether costimulatory molecules, including CD28, cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and programmed death-1 (PD-1), are expressed on peripheral blood lymphocytes (PBLs) of canine patients with histiocytic sarcoma. The objective of this study was to evaluate the expression of CD28, CTLA-4, and PD-1 molecules on PBLs of patients with histiocytic sarcoma, patients with other tumors, and healthy controls. Twenty-six dogs were included in the study, with eight, ten, and eight dogs in the histiocytic sarcoma, other tumor, and healthy control groups, respectively. PBLs and serum were prospectively obtained from patients diagnosed histopathologically with histiocytic sarcoma, other tumors and healthy controls. The surface expression of CTLA-4, CD28, and PD-1 on T lymphocytes was examined using flow cytometric analysis. Serum samples were frozen at -30°C until serum interferon-γ (IFN-γ) was measured by enzyme-linked immunosorbent assay. The expression level of CTLA-4 on CD4+ lymphocytes was significantly higher in the histiocytic sarcoma group than in the control group. The expression of CTLA-4 on CD8+ lymphocytes was significantly higher in the histiocytic sarcoma group than in the other two groups. In addition, the expression of PD-1 on CD8+ lymphocytes was significantly higher in the histiocytic sarcoma group than in the control group. However, no significant differences in CD28 expressions and serum IFN-γ levels were observed. The present results provided evidence showing that the expression levels of CTLA-4 on both CD4+ and CD8+ lymphocytes and PD-1 on CD8+ lymphocytes in peripheral blood obtained from dogs with histiocytic sarcoma were upregulated. The overexpressions of CTLA 4 and PD-1 suggested that antitumor immunity may be suppressed in dogs with histiocytic sarcoma.

Introduction: Histiocytic sarcoma (HS) of the central nervous system (CNS) is exceptionally rare in pediatric patients, historically associated with an exceptionally poor prognosis. Here, the authors present a novel case of protracted progression-free survival following surgical excision, radiotherapy and temozolomide., Case Report: A 15-year-old Caucasian girl presented with a two-month history of headache, diplopia, vomiting, lethargy, weight loss and neurocognitive deterioration without gross neurological deficit on physical examination. Magnetic resonance imaging (MRI) of the brain identified a 5.8 × 4.7 × 4.0 cm lesion in the right frontal lobe with associated mass effect and no dissemination. Following two surgical procedures, gross total resection was achieved. Histology and immunohistochemistry confirmed HS, with strong CD163 staining. After focal radiotherapy with concomitant temozolomide, and a further seven cycles of temozolomide, the patient made an excellent recovery and is recurrence free without neurological deficit, 23 months following presentation., Conclusion: To the authors' knowledge, this is the first incidence of a prolonged, functionally preserved and recurrence-free outcome following a diagnosis of HS within the CNS of a pediatric patient. We suggest early diagnosis prior to dissemination and complete surgical resection as an essential treatment goal in this rare disease.