Banca de QUALIFICAÇÃO: BARTOLOMEU BENEDITO NEVES DOS SANTOS

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : BARTOLOMEU BENEDITO NEVES DOS SANTOS
DATE: 19/02/2024
TIME: 09:00
LOCAL: Anfiteatro do Anexo I do Instituto de Veterinária
TITLE:

Immunodetection of the α Chain of Interleukin-3 Receptor in Canine Cutaneous Mast Cell Tumors of Low and High Grade.

KEY WORDS:

Immunohistochemistry, prognosis, CD123, c-Kit, standardization, câncer

PAGES: 55
BIG AREA: Ciências Agrárias
AREA: Medicina Veterinária
SUBÁREA: Patologia Animal
SPECIALTY: Anatomia Patologia Animal
SUMMARY:

Canine cutaneous mastocytoma (CCM) is one of the most common neoplasms in dogs and its prognosis is highly variable. Although there are histological grading methods, immunohistochemical markers, and molecular analyses to aid in the prognosis of most cases, there is no way to predict the behavior of all CCM cases, especially the most common, Patnaik Grade II/Kiupel Low Grade. Additionally, the main complementary immunohistochemical prognostic methods suffer from the variety of methodologies used and the lack of standardization in the veterinary literature. The alpha chain of the interleukin-3 receptor (CD123) has been extensively studied in human medicine as a diagnostic marker for hematolymphoid neoplasms and marks some cases of various human mastocytosis, being pointed out as a prognostic factor in some studies. This marker is still being tested in various experiments as a therapeutic target for human neoplasms, especially refractory/recurrent leukemias and plasmacytoid dendritic cell neoplastic diseases. Despite the apparent great potential of this biomarker in human medicine, in veterinary medicine it had not yet been reported in studies that clearly demonstrated its detection in canine samples. This study, based on a sample of 63 CCMs, 30 of low grade and 33 of high grade, demonstrated that 57.1% (36/63) of cases were immunostained with CD123, with 36.1% (13/30) of low-grade cases and 63.9% (23/33) of high-grade cases. In addition, we analyzed the intensity of staining in positive cases at three levels (weak, moderate, and strong). Immunostaining of CCMs with CD123 was positively correlated with high Kiupel Grade (p = 0.034) and the intensity of immunostaining was positively correlated with strong intensity in high-grade CCMs (p = 0.032). Prior to this result, we demonstrated a whole methodology of standardization, from the verification of reaction of a monoclonal versus polyclonal antibody with different detection systems and comparison with staining in human controls. We also investigated the immunodetection of CD123 in various non-neoplastic canine tissues such as: intestines, stomach, pancreas, kidney, liver, lung, spleen, lymph node, palatine tonsil, central nervous system, adrenal gland, mammary gland, and salivary gland, as well as neoplastic samples in TMA containing 2mm cores of specimens of cutaneous plasmacytomas, cutaneous histiocytomas, histiocytic sarcomas, and canine lymphomas. Finally, we demonstrated that the two-step polymer immunohistochemical detection method can interfere with the KIT staining pattern in CCMs, where cases immunostained as standard in the one-step polymer detection method, showed as a III in the two-step detection method, which infers a major change in the interpretation of prognosis dependent on this technique.

COMMITTEE MEMBERS:
Interna - 6387102 - MARILENE DE FARIAS BRITO QUEIROZ
Interna - 3247698 - TICIANA DO NASCIMENTO FRANCA
Interna - 2606155 - VIVIAN DE ASSUNCAO NOGUEIRA CARVALHO
Externa à Instituição - VALIRIA CERQUEIRA DUARTE - UFPA