PD-L1 and MCL-1 markers and the relationship with prognostic characteristics of differentiated thyroid carcinoma

Author(s)

Zantut-Wittmann, Denise Engelbrecht ; Barreto, Icleia Siqueira ; Laus, Ana Carolina ; Moreno, Daniel Antunes ; Moma, Camila Aparecida ; Ribeiro Maia, Frederico Fernandes ; Montali da Assumpcao, Ligia Vera ; Reis, Rui Manuel

• Document type: Journal article
• Source: Molecular and Cellular Endocrinology; v. 570, p. 8-pg., 2023-06-15.

Abstract

Objectives: MCL-1 and PD-L1 proteins are related to carcinogenesis mechanisms in differentiated thyroid carcinoma(DTC). Tumor antigens stimulate the expression of PD-1 in immune cells, which binds to PD-L1 of tumor cells, inducing immune escape from the tumor. MCL-1, an anti-apoptotic member of the BCL-2 family, is necessary for the survival of T and B lymphocytes and has a high oncogenic potential. We aim to evaluate the clinical utility and relevance of MCL-1 and PD-L1 in the long-term prognosis of DTC. Methods: 120 DTC patients after total thyroidectomy and radioiodine therapy followed for a minimum of 2 years were included. Demographic features, tumor histopathology, persistence/recurrence risk, factors associated with outcome, initial response to therapy, persistence or disease-free at the follow-up were related to MCL-1 and PD-L1 immunohistochemical expression and BRAFV600E mutation. Results: 100(83.3%) were women, 46.64 +/- 16.73 years old at diagnosis; 37(30.8%) patients were at high, 45 (37.5%) of intermediate and 38(31.7%) of low disease recurrence/persistence risk. At the end of follow-up of 124.86 +/- 65.36 months, 48(42.5%) had persistent disease. 103(85.8%) patients had papillary thyroid carcinoma (PTC), 17(14.2%) follicular thyroid carcinoma (FTC). In PTC, moderate/strong PD-L1 and MCL-1 expressions were associated to BRAFV600E (p=0.0467; p=0.0044). PD-L1 was also associated with tall cell subtype (p=0.0274). In FTC, weak PD-L1 expression was associated to the largest nodule diameter (p=0.0100). Strong/moderate PD-L1 expression was associated to T2 and the weak expression with T3 in TNM classification (p=0.0490). Moderate MCL-1 expression was associated to smoking (p=0.0350). Conclusions: PDL-1, marker of progression of tumor cells and MCL-1, anti-apoptotic marker, were associated with PTC carrying BRAFV600E mutation, while PDL-1 was associated with more aggressive PTC subtype. MCL-1 and PD-L1 could be useful in composing a panel to assess the prognosis of PTC patients. On the other hand, both markers seemed to have lower relevance to FTC patients. (AU)

• FAPESP's process: 17/19663-0 - ROLE OF MCL-1 , PDL-1 AND KI-67 IN TUMOR PROGRESSION, RECURRENCE AND OUTCOMES IN ADVANCED THYROID CANCER.
• Grantee: Denise Engelbrecht Zantut Wittmann
• Support Opportunities: Regular Research Grants