Critical Analysis of the Impact of Second Harmonic Generation Microscopy on Medullary Thyroid Carcinoma: From Benchtop to Clinical Applications.

• Grant number: 23/12601-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2024
• End date: December 31, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Lucas Leite Cunha
• Grantee: Jean Ferrante Mariano
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 21/02752-6 - Multiple Endocrine Neoplasia type 2 (MEN 2) and Medullary Thyroid Carcinoma (TCM): new issues in developmental biology, genetics, immunology, epidemiology, mechanisms of disease and clinical management, AP.TEM

Abstract

The present study is linked to the ongoing Thematic Project (2021/02752-6), directly contributing to subproject 3 of this Thematic Project, which aims to investigate the physiopathological mechanisms of medullary thyroid carcinoma (MTC) in patients with multiple endocrine neoplasia type 2 (MEN2). The most important and predominant clinical manifestation of patients with MEN2 is MTC. It is possible that the clinical peculiarities of MTC have molecular and immunological explanations in the unique composition of the immune response present in the tumor microenvironment of these patients. Therefore, our objectives are to investigate the impact of second harmonic generation (SHG) microscopy on the prognosis of patients with MTC and MEN2, as well as to describe the profile of the immune response present in the tumor microenvironment of patients with MTC. This study is a translational study aimed at unraveling the mechanisms by which immune system cells interact in the composition of the tumor microenvironment and the collagen fiber profile of MTC.We will include 50 patients with MTC. Samples from these 50 patients will be obtained, including paraffin-preserved tissues. The investigation of the collagen fiber profile will be conducted using SHG microscopy technology. The investigation of the immunological profile of the microenvironment will be performed using immunohistochemistry techniques. Variables derived from the collagen fiber profile, as well as the profile of immune cell infiltration, will be compared among patients with different tumor aggressiveness profiles and clinical outcomes. Event-free survival will be calculated using Kaplan-Meier survival curves with log-rank analysis. A multivariate logistic regression model will be applied using clinical variables, collagen fiber profile, and immunological variables as independent variables and clinical events as dependent variables. All tests will be conducted with a significance level of p<0.05. We believe that this could bring new prognostic markers that aid in the individualization of clinical management for patients with MTC. It is possible that a better understanding of the immune mechanisms in the MTC microenvironment may uncover new therapeutic targets that could lead to the development of new drugs and immunotherapies.