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

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.

Usefulness of pre-thyroidectomy neutrophil-lymphocyte, platelet-lymphocyte, and monocyte-lymphocyte ratios for discriminating lymph node and distant metastases in differentiated thyroid cancer.

OBJECTIVE: This study aimed to analyze the relationship of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) with clinicopathological characteristics of patients with differentiated thyroid cancer (DTC). METHODS: This retrospective study included 390 patients with DTC who had complete blood cell counts available at the time of surgery. NLR, PLR, and MLR were calculated, and the risk of cancer-related death, structural recurrence, and response to therapy were assessed using the eighth edition of the tumor-node-metastasis classification, American Thyroid Association (ATA) Risk Stratification System, and ATA Response to Therapy Reclassification, respectively. RESULTS: PLR was higher in patients with distant metastasis than in those without (133.15±43.95 versus 119.24±45.69, p=0.0345) and lower in patients with disease-free status (117.72±44.70 versus 131.07±47.85, p=0.0089) than in those who experienced persistent disease or death. Patients aged ≥55 years had a higher MLR than those aged <55 years (0.26±0.10 versus 0.24±0.12, p=0.0379). Higher MLR (odds ratio [OR]: 8.775, 95% confidence interval [CI]: 1.532-50.273, p=0.0147), intermediate ATA risk (OR: 4.892, 95% CI: 2.492-9.605, p≤0.0001), and high ATA risk (OR: 5.998, 95% CI: 3.126-11.505, p≤0.0001) were risk factors associated with active disease. NLR was not significantly different among the studied variables. Receiver operating characteristic curve cut-off values for NLR, PLR, and MLR were able to differentiate distant metastasis from lymph node metastasis (NLR>1.93: 73.3% sensitivity and 58.7% specificity, PLR>124.34: 86.7% sensitivity and 69.2% specificity, MLR>0.21: 80% sensitivity and 45.2% specificity). CONCLUSION: Cut-off values of NLR, PLR, and MLR differentiated distant metastasis from lymph node metastasis with good sensitivity and accuracy. PLR was associated with disease-free status and it was higher in DTC patients with distant metastasis, persistent disease, and disease-related death. MLR was a risk factor for active disease.

Usefulness of pre-thyroidectomy neutrophil-lymphocyte, platelet-lymphocyte, and monocyte-lymphocyte ratios for discriminating lymph node and distant metastases in differentiated thyroid cancer

OBJECTIVE: This study aimed to analyze the relationship of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) with clinicopathological characteristics of patients with differentiated thyroid cancer (DTC). METHODS: This retrospective study included 390 patients with DTC who had complete blood cell counts available at the time of surgery. NLR, PLR, and MLR were calculated, and the risk of cancer-related death, structural recurrence, and response to therapy were assessed using the eighth edition of the tumor-node-metastasis classification, American Thyroid Association (ATA) Risk Stratification System, and ATA Response to Therapy Reclassification, respectively. RESULTS: PLR was higher in patients with distant metastasis than in those without (133.15±43.95 versus 119.24±45.69, p=0.0345) and lower in patients with disease-free status (117.72±44.70 versus 131.07±47.85, p=0.0089) than in those who experienced persistent disease or death. Patients aged ≥55 years had a higher MLR than those aged <55 years (0.26±0.10 versus 0.24±0.12, p=0.0379). Higher MLR (odds ratio [OR]: 8.775, 95% confidence interval [CI]: 1.532-50.273, p=0.0147), intermediate ATA risk (OR: 4.892, 95% CI: 2.492-9.605, p≤0.0001), and high ATA risk (OR: 5.998, 95% CI: 3.126-11.505, p≤0.0001) were risk factors associated with active disease. NLR was not significantly different among the studied variables. Receiver operating characteristic curve cut-off values for NLR, PLR, and MLR were able to differentiate distant metastasis from lymph node metastasis (NLR>1.93: 73.3% sensitivity and 58.7% specificity, PLR>124.34: 86.7% sensitivity and 69.2% specificity, MLR>0.21: 80% sensitivity and 45.2% specificity). CONCLUSION: Cut-off values of NLR, PLR, and MLR differentiated distant metastasis from lymph node metastasis with good sensitivity and accuracy. PLR was associated with disease-free status and it was higher in DTC patients with distant metastasis, persistent disease, and disease-related death. MLR was a risk factor for active disease.