Immunolabelling of Acetylated Histones 3 and 4 and Histone Deacetylases 1, 2 and 6 in Canine Soft Tissue Sarcomas.

The objective of this study was to investigate the immunolabelling of acetylated histones and histone desacetylase (HDAC) enzymes in canine soft tissue sarcomas (STSs) and to correlate them with histological and clinical features in order to identify possible prognostic and therapeutic targets in these neoplasms. Fifteen canine STS samples were evaluated and were submitted to immunohistochemistry for acetylated histones 3 (H3) and 4 (H4) and deacetylating enzymes (HDAC1, HDAC2 and HDAC6). Intense immunolabelling of H4 was seen in comparison with H3. A strong positive correlation was observed between the H3 intensity score and the number of mitotic figures (P = 0.004, r = 0.7). Intense immunolabelling of HDAC1 was found in comparison to the expression of HDAC2 and HDAC6 in the evaluated STSs. This finding suggests that HDAC1 may be a potential target for HDAC inhibitors in STSs in dogs.

Liquid biopsy based on small extracellular vesicles predicts chemotherapy response of canine multicentric lymphomas.

Lymphoma is the most common type of canine hematological malignancy where the multicentric (cMCL) form accounts for 75% of all cases. The standard treatment is the CHOP chemotherapy protocols that include cyclophosphamide, doxorubicin, vincristine and prednisone, where the majority of dogs achieve complete/partial response; however, it is very important to predict non-responsive cases to improve treatment and to develop new targeted therapies. Here we evaluate a liquid biopsy approach based on serum Small Extracellular Vesicles enriched for exosomes (SEVs) to predict cMCL chemotherapy response. Nineteen dogs at the end of the 19-week chemotherapy protocol (8 Complete Response and 11 Progressive Disease) were evaluated for serum SEVs size, concentration and screened for 95 oncomirs. PD patients had higher SEVs concentration at the diagnosis than CR patients (P = 0.034). The ROC curve was significant for SEVs concentration to predict the response to CHOP (AUC = 0.8011, P = 0.0287). A potential molecular signature based on oncomirs from SEVs (caf-miR-205, caf-miR-222, caf-mir-20a and caf-miR-93) is proposed. To the best of our knowledge, this is the first study demonstrating the potential of a liquid biopsy based on SEVs and their miRNAs content to predict the outcome of chemotherapy for canine multicentric lymphomas.