Banca de DEFESA: BARTOLOMEU BENEDITO NEVES DOS SANTOS

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : BARTOLOMEU BENEDITO NEVES DOS SANTOS
DATE: 21/03/2024
TIME: 09:00
LOCAL: Anexo I do Instituto de Veterinária
TITLE:

Evaluation of Immunodetection of the α Chain of Interleukin-3 Receptor (CD123) in Canine Cutaneous Mast Cell Tumors of Low and High Grade: Protocol Development and Impact of KIT Detection Method

KEY WORDS:

Immunohistochemistry, prognosis, c-Kit, standardization, cancer

PAGES: 91
BIG AREA: Ciências Agrárias
AREA: Medicina Veterinária
SUBÁREA: Patologia Animal
SPECIALTY: Anatomia Patologia Animal
SUMMARY:

Canine cutaneous mast cell tumor (MCTs) is one of the most common neoplasms in dogs, with a highly variable prognosis. Despite the existence of histological grading methods, immunohistochemical markers, and molecular analyses to aid in the prognosis of most cases, there is no means to predict the behavior of all MCTs cases, especially those most frequent, Grade II Patnaik/Low Grade Kiupel. Additionally, the main complementary methods of prognostic immunohistochemistry (IHC) for MCTs suffer from the variety of methodologies employed in the literature and consequently from the lack of standardization and consensus on these methodologies. The α chain of the interleukin-3 receptor (CD123), which has been studied in Human Medicine as a diagnostic marker for lymphohematopoietic neoplasms, is immunodetected in some human mastocytosis cases and is suggested as a prognostic factor. This marker has also been extensively tested in various experiments as a therapeutic target for human neoplasms, particularly refractory/relapsed leukemias and blastic plasmacytoid dendritic cell neoplasms. Despite the apparent potential of this biomarker in Human Medicine, it had not been reported in Veterinary Medicine studies demonstrating its clear detection in canine samples. This research, based on a sample of 63 MCTs (30 low-grade and 33 highgrade), demonstrated that 58.7% (37/63) of cases were immunoreactive with CD123, with 43.3% (13/30) of low-grade cases and 72.7% (24/33) of high-grade cases being positive. Additionally, we analyzed the intensity of immunostaining in positive cases at two levels (weak and consistent). Immunostaining of MCTs with CD123 was positively related to high Kiupel Grade (p = 0.020), and the intensity of immunostaining showed a positive relationship for consistent staining in high-grade Kiupel MCTs (p < 0.001). Prior to this result, we demonstrated an extensive methodology of standardization and validation by comparing CD123 staining patterns, from checking the reaction of a monoclonal versus polyclonal anti-CD123 antibody with different detection systems and comparing with the staining pattern in human controls. We also investigated CD123 immunodetection in various non-neoplastic canine tissues and samples of benign and malignant lymphohematopoietic neoplasms on a TMA slide with 2mm cores of specimens from cutaneous plasmacytomas, cutaneous histiocytomas, histiocytic sarcomas, and multiple myeloma. Finally, we demonstrated that the two-step polymer IHC detection method may interfere with the KIT staining pattern in MCTs, where cases immunostained as KIT patterns I and II in the one-step polymer detection method were shown as a pattern KIT III in the two-step polymer detection method, which implies a significant change in the interpretation of prognosis depending on this technique.

COMMITTEE MEMBERS:
Presidente - 3247698 - TICIANA DO NASCIMENTO FRANCA
Interna - 2606155 - VIVIAN DE ASSUNCAO NOGUEIRA CARVALHO
Interna - 6387102 - MARILENE DE FARIAS BRITO QUEIROZ
Externa ao Programa - 3377607 - APARECIDA ALVES DO NASCIMENTO - UFRRJExterna à Instituição - SAMAY ZILLMANN ROCHA COSTA
Externo à Instituição - PEDRO SOARES BEZERRA JUNIOR - UFPA
Externa à Instituição - VALIRIA CERQUEIRA DUARTE - UFPA
Externo à Instituição - DAVID DRIEMEIER - UFRGS