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School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
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Saint Vincent’s Clinical School, UNSW Sydney, Sydney, Australia
SydPath, Saint Vincent’s Hospital, Sydney, Australia
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Gene & Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, New South Wales, Australia
Faculty of Medicine & Health, The University of Sydney, Camperdown, New South Wales, Australia
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School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
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School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
School of Medicine, University of Wollongong, New South Wales, Australia
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School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
Department of Head & Neck Surgery, Liverpool Hospital, Liverpool, New South Wales, Australia
Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia
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School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
South West Sydney Clinical School, UNSW Sydney, Sydney, Australia
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Programmed cell death-ligand 1 (PD-L1) has recently been shown to play a role in the regulation of epithelial-to-mesenchymal transition (EMT); however, the relationship between PD-L1 expression, EMT and the inflammatory tumour microenvironment has yet to be investigated in thyroid cancer. To address this issue, we examined the expression of CD8, PD-L1 and the EMT markers E-cadherin and vimentin in a cohort of 74 papillary thyroid cancer (PTC) patients and investigated the association of these with clinicopathologic characteristics and disease-free survival (DFS). The relationship between PD-L1 and EMT was further examined in three thyroid cancer cell lines via Western blot and live cell imaging. In order to expand our in vitro findings, the normalised gene expression profiles of 516 thyroid cancer patients were retrieved and analysed from The Cancer Genome Atlas (TCGA). PD-L1 positivity was significantly higher in PTC patients exhibiting a mesenchymal phenotype (P = 0.012). Kaplan–Meier analysis revealed that PD-L1 (P = 0.045), CD8 (P = 0.038) and EMT status (P = 0.038) were all significant predictors for DFS. Sub-analysis confirmed that the poorest DFS was evident in PD-L1 positive patients with EMT features and negative CD8 expression (P < 0.0001). IFN-γ treatment induced upregulation of PD-L1 and significantly promoted an EMT phenotype in two thyroid cancer cell lines. Our findings suggest that PD-L1 signalling may play a role in stimulating EMT in thyroid cancer. EMT, CD8 and PD-L1 expression may serve as valuable predictive biomarkers in patients with PTC.
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Imperial College Healthcare NHS Trust, London, UK
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Imperial College Healthcare NHS Trust, London, UK
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Imperial College Healthcare NHS Trust, London, UK
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Imperial College Healthcare NHS Trust, London, UK
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Imperial College Healthcare NHS Trust, London, UK
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Purpose
To review the clinical and biochemical characteristics and clinical outcome of patients presenting with pituitary apoplexy to a tertiary centre.
Methods
We retrospectively reviewed the clinical features, predisposing factors, biochemistry and clinical outcome of patients presenting with pituitary apoplexy to Imperial College Healthcare NHS Trust between 1991 and 2015.
Results
We identified 64 patients with pituitary apoplexy (more complete clinical records were available in 52 patients). The median age at presentation was 46.7 years (IQR 31.5–57.0 years). Pituitary apoplexy was the first presentation of pituitary disease in 38/52 of patients and predisposing factors were identified in 28/52. Pituitary apoplexy predominantly occurred in patients with non-functioning pituitary adenomas (47/52). Headache was most commonly described as sudden onset, severe, lateralising to the frontal or temporal regions. Symptoms of meningeal irritation were reported in 7/18 and visual abnormalities in 22/35. A pre-treatment serum cortisol <100 nmol/L was recorded in 12/31 of patients. All patients with visual disturbance had some resolution of their visual symptoms whether managed surgically (14/14) or conservatively (5/5), although pituitary endocrine function did not fully recover in any patient.
Conclusions
In conclusion, these data describe the clinical features of pituitary apoplexy to aid the clinician in diagnosing this rare emergency presentation of pituitary disease. Prospective multicentre studies of the presentation of pituitary apoplexy are required to further characterise presentation and outcomes.
