Abstract:BackgroundMedullary thyroid cancer (MTC) comprises only 4% of all thyroid cancers and originates from the parafollicular C-cells. HIF-1α expression has been implied as an indicator of worse prognosis in various solid tumors. However, whether expression of HIF-1α is a prognosticator in MTC remained unclear. Our aim was to evaluate the prognostic value of HIF-1α in patients with MTC.MethodsAll patients with MTC who were operated on between 1988 and 2014 in five tertiary referral centers in The Netherlands were i… Show more
“…This study was performed according to national guidelines with respect to the use of leftover tissue and approval for this study, including the use of patient data, was obtained from the Institutional Review Board of the UMCU [ 7 , 19 ].…”
Section: Methodsmentioning
confidence: 99%
“…1 . Data on hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), glucose transporter 1 (Glut-1), carbonic anhydrase IX (CAIX) and microvessel density (MVD) was available from a previous study [ 7 ]. Fig.…”
Section: Methodsmentioning
confidence: 99%
“…Unfortunately, approximately 45% of patients present with metastases (stage III and IV), associated with 10-year survival rates of 71% and 21%, respectively [ 3 ]. Prognosis is difficult to predict in stage III or IV MTC, whereas this is essential for personalised follow-up and adjuvant therapy strategies for patients that will rapidly progress [ 7 ].…”
PurposeMedullary thyroid carcinoma (MTC) derives from the parafollicular C-cells of the thyroid gland. Somatostatin receptors (SSTRs) are expressed in various neuroendocrine tumours including MTC. The aim of this study was to evaluate SSTR2A as a prognostic factor for MTC, to study distribution of SSTR2A expression within tumours and to compare expression of SSTR2A between primary tumours and corresponding lymph node metastases.MethodsPatients who underwent surgery between 1988 and 2014 for MTC from five tertiary referral centres in The Netherlands were included. In total, primary tumours of 114 patients and lymph node metastases of 34 patients were analysed for expression of SSTR2A using a tissue microarray, and correlated with clinicopathological variables and survival.ResultsThe mean age of patients was 45.5 years (SD 16.2), 55 patients were male (49.5%). Primary tumours of 58 patients (50.9%) showed SSTR2A expression. In multivariate Cox-regression analysis, SSTR2A positivity correlated independently with better overall survival (OS) (HR 0.3; 95% CI 0.1–1.0). In stage IV MTC patients, 10-year survival rates for SSTR2A-negative and positive patients were 43% and 96%, respectively. In 53.9% of patients with lymph node metastases, expression in primary tumour and lymph node metastases differed.ConclusionSSTR2A expression is correlated with longer OS in MTC, especially for stage IV patients, suggesting that SSTR2A expression might be a useful prognostic factor in MTC. The SSTR2A status of the primary MTC does not predict expression in lymph node metastases.
“…This study was performed according to national guidelines with respect to the use of leftover tissue and approval for this study, including the use of patient data, was obtained from the Institutional Review Board of the UMCU [ 7 , 19 ].…”
Section: Methodsmentioning
confidence: 99%
“…1 . Data on hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), glucose transporter 1 (Glut-1), carbonic anhydrase IX (CAIX) and microvessel density (MVD) was available from a previous study [ 7 ]. Fig.…”
Section: Methodsmentioning
confidence: 99%
“…Unfortunately, approximately 45% of patients present with metastases (stage III and IV), associated with 10-year survival rates of 71% and 21%, respectively [ 3 ]. Prognosis is difficult to predict in stage III or IV MTC, whereas this is essential for personalised follow-up and adjuvant therapy strategies for patients that will rapidly progress [ 7 ].…”
PurposeMedullary thyroid carcinoma (MTC) derives from the parafollicular C-cells of the thyroid gland. Somatostatin receptors (SSTRs) are expressed in various neuroendocrine tumours including MTC. The aim of this study was to evaluate SSTR2A as a prognostic factor for MTC, to study distribution of SSTR2A expression within tumours and to compare expression of SSTR2A between primary tumours and corresponding lymph node metastases.MethodsPatients who underwent surgery between 1988 and 2014 for MTC from five tertiary referral centres in The Netherlands were included. In total, primary tumours of 114 patients and lymph node metastases of 34 patients were analysed for expression of SSTR2A using a tissue microarray, and correlated with clinicopathological variables and survival.ResultsThe mean age of patients was 45.5 years (SD 16.2), 55 patients were male (49.5%). Primary tumours of 58 patients (50.9%) showed SSTR2A expression. In multivariate Cox-regression analysis, SSTR2A positivity correlated independently with better overall survival (OS) (HR 0.3; 95% CI 0.1–1.0). In stage IV MTC patients, 10-year survival rates for SSTR2A-negative and positive patients were 43% and 96%, respectively. In 53.9% of patients with lymph node metastases, expression in primary tumour and lymph node metastases differed.ConclusionSSTR2A expression is correlated with longer OS in MTC, especially for stage IV patients, suggesting that SSTR2A expression might be a useful prognostic factor in MTC. The SSTR2A status of the primary MTC does not predict expression in lymph node metastases.
“…Hypoxia-inducible factor-1α (HIF-1α) is a major transcription factor involved in the hypoxic response of cancer cells and activates hundreds of genes that play vital roles in angiogenesis, proliferation, glucose metabolism, invasion and metastasis, and resistance to radiation and chemotherapy in HCC [18] . Several studies demonstrated that high HIF-1α expression in tumor tissue is associated with poor outcomes in multiple types of cancer, including HCC [20] , [21] , [22] . Recently, relevant studies exhibited that HIF-1α upregulates PD-L1 expression on myeloid-derived suppressor cells and tumor cells, contributing to cancer immune evasion [23] , [24] , [25] , [26] .…”
OBJECTIVE: To investigate the correlation between the expression of PD-L1 and HIF-1α in hepatocellular carcinoma (HCC) tissue and further analyze the association with clinical parameters and the prognostic value of coexpression in HCC patients. METHODS: We assessed the expression of PD-L1 and HIF-1α by immunohistochemistry in tumor tissue from 90 HCC patients who underwent curative hepatectomy. The results were validated in an independent cohort of additional 90 HCC patients. RESULTS: PD-L1 and HIF-1α exhibited in tumor tissue high expression rates of 41.11% (37/90) and 43.33% (43/90), respectively, and their expressions were positively correlated (r = 0.563, P < .01). High expression of PD-L1 was significantly associated with low albumin levels (P < .05); high expression of HIF-1α was significantly correlated with high alpha-fetoprotein (AFP) levels and low albumin levels (P < .05); high expression of both PD-L1 and HIF-1α was also significantly associated with high AFP levels and low albumin levels (P < .05). High expression of PD-L1, HIF-1α, as well as both PD-L1 and HIF-1 α was respectively significantly associated with worse overall survival (OS) and disease-free survival (DFS) (P < .05). Patients with co-overexpression of PD-L1 and HIF-1α had the worst prognosis compared with other groups. Additionally, multivariate Cox regression models suggested that high expression of PD-L1, HIF-1α, as well as both PD-L1 and HIF-1α was an independent prognostic factor for OS and DFS (P < .05). Furthermore, the positive correlation and prognostic values of PD-L1 and HIF-1α were validated in an independent data set. CONCLUSION: We demonstrated that HCC patients with co-overexpression of PD-L1 and HIF-1α in tumor tissue had a significantly higher risk of recurrence or metastasis and death compared with others. Therefore, more frequent follow-up is needed for patients with co-overexpression of PD-L1 and HIF-1α. At the same time, a combinational therapy with HIF-1α inhibitors in conjunction with PD-L1 blockade may be beneficial for HCC patients with co-overexpression in the future.
“…Expression of HIF-1alpha is another prognostic marker. Positive expression has been shown to be associated with worse 5-year survival and progression free survival [107]. Stem cell markers CD133 and CD44 are unfavourable prognostic predictors.…”
Section: Immunohistochemistry Of Thyroid Neoplasmsmentioning
Thyroid nodules are frequent in general population, found in 3.7-7% of people by palpation and 42-67% by ultrasonography (US). The differential diagnosis ranges from papillary (PC), follicular (FC) and medullary (MC) carcinomas to follicular adenoma (FA) and colloid goitre. Cancer risk in thyroid nodules varies: 5% in masses found by palpation, 1.6-15% by US, 3.9-11.3% by computed tomography (CT), 5-6% by magnetic resonance imaging (MRI) and 30-50% by positron emission tomography (PET). The final diagnosis depends on fine needle aspiration (FNA) findings and histopathology. The recent WHO classification (2017) is based on classic morphology, including assessment of invasion and nuclei. New entities are defined to designate tumours with doubtful invasion or controversial nuclear features. By immunohistochemistry, PC expresses HBME-1, TROP-2, CITED1 and CK19. Notably, PC can stain for CD20. MC is recognised by neuroendocrine differentiation. To distinguish FA vs. FC, evaluation of HBME-1, p27 and galectin has been suggested. Regarding miRNAs, miR-146b, miR-222, miR-221 and miR-181b are upregulated, while miR-145, miR-451, miR-613 and miR-137 are downregulated in PC. FC features downregulated miR-199a-5p and upregulated miR-197 and miR-346. In MC, miR-21 and miR-129-5p are downregulated. In addition, increased systemic inflammatory reaction can be poor prognostic factor in thyroid cancer. The aim of this chapter is to review classic and innovative histopathology of thyroid nodules for diagnostic pathology practice and research in multidisciplinary thyroid teams.
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