Endocrine Abstracts

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 and has a high oncogenic potential. The relationship of these markers with prognosis in DTC remains unknown. We aim to evaluate the clinical utility of immunohistochemical expression (IHC) of markers MCL-1 and PD-L1 in DTC and to investigate its relevance in the long-term prognosis.

Methods: 120 patients with DTC after total thyroidectomy and radioiodine therapy followed for a minimum of 2 years after complete treatment were included. Demographic features, tumors histopathological characteristics, initial risk classification of persistence/recurrence, factors associated with outcome, initial response to therapy, persistence or disease-free at the end of follow-up were evaluated. These data were related to IHC expression of MCL-1 and PD-L1 and presence of BRAFV600E mutation.

Results: Among the patients, 100(83.33%) were women and 20 men, age at diagnosis 46.64±16.73 years; 37 (30.8%) patients were at high risk, 45(37.5%) of intermediate risk and 38(31.7%) of low risk of disease recurrence/persistence. At the end of follow-up, 65(57.5%) were disease-free and 48(42.5%) had persistent disease. The largest tumor diameter was 2.99±1.79 cm; 103(85.8%) patients had papillary thyroid carcinoma (PTC) and 17(14.2%) had follicular thyroid carcinoma (CFT), with a follow-up time of 124.86±65.36 months. BRAF V600E mutation was detected in 49 (59.8%) patients and absent in 33(40.2%). Strong/moderate expression of PD-L1 was associated to tall cell variant PTC (P=0.0274). Strong MCL-1 expression was associated with the presence of the BRAF V600E mutation (P = 0.0468); and weak expression of MCL-1 was associated with multifocality (P = 0.0290). No patients with CFT presented weak MCL-1 expression, and all tumors with weak expression were PTC (P = 0.0409).

Conclusions: PDL-1, marker of higher proliferation and progress of tumor cells was associated with more aggressive PTC variant. The anti-apoptotic marker MCL-1 was associated with CDT carrying the BRAFV600E mutation. Additionally, lower anti-apoptotic marker expression was related to multifocal and papillary thyroid cancer. Additional studies are needed to confirm the possible role of these markers in the tumorigenesis and evolution of DTC.