SFEBES2022 Oral Communications Endocrine Cancer and Late Effects (6 abstracts)
Delta-like non-canonical Notch ligand 1 (DLK1) – a novel biomarker in adrenocortical carcinoma
James Pittaway 1 , Katia Mariniello 1 , Barbara Altieri 2 , Iuliu Sbiera 2 , Silviu Sbiera 2 , Teng-Teng Chung 3 , Tarek Abdel-Azziz 3 , Aimee DiMarco 4 , Fausto Palazzo 4 , Scott A. Akker 1 , Laura-Sophie Landwehr 2 , Cristina Ronchi 2,5 , Laila Parvanta 1 , William Drake 1 , Matthias Kroiss 2 , Martin Fassnacht 2 & Leonardo Guasti 1
1Barts and The London School of Medicine and Dentistry, London, United Kingdom; 2University Hospital Würzburg, Würzburg, Germany; 3University College Hospital, London, United Kingdom; 4Hammersmith Hospital, Imperial College London, London, United Kingdom; 5Institute of Metabolism and System Research, Birmingham, United Kingdom
Adrenocortical carcinoma (ACC) is a rare malignancy with limited treatment options and a heterogenous prognosis. The histological diagnosis of ACC is complex and there is increasing interest in identifying and validating new immunohistochemical markers. Delta-like non-canonical Notch ligand 1 (DLK1) is a cleavable single-pass transmembrane protein. In humans, DLK1 is present in many tissues during foetal development, is restricted to progenitor/stem cells in a few adult tissues but is expressed in numerous malignancies. We have previously shown that DLK1 is overexpressed in ACC compared to normal adrenal gland and aldosterone producing adenomas. In a validation cohort of 196 ACC tumour samples (149 primary, 47 secondary), we have found that DLK1 is expressed in 96% of samples. Level of expression is independent of ENSAT stage, Ki67 index or hormonal activity of the tumour and consistent in primary and secondary disease in the same patients (P=0.034). Additionally, higher levels of DLK1 expression (above vs below median) are associated with a two-fold increased risk of disease recurrence after surgery (HR 1.93, P=0.042). Furthermore, we have found that serum DLK1 levels are detectable in patients with ACC and in an initial cohort are significantly higher in patients with ACC (mean=20.41ng/ml, n=8) than patients undergoing adrenalectomy for other suspected adrenocortical pathologies (mean=13.14ng/ml, n=27; P=0.0003). Pre-operative DLK1 serum levels can predict the diagnosis of ACC with a high level of specificity and sensitivity (ROC AUC = 0.8796; CI 0.7590 – 1.000, P=0.0013). Finally, raised serum DLK1 levels in ACC patients are significantly reduced post-operatively (17.55 to 10.77ng/ml, n=4; P=0.0123). Our data suggest that DLK1 expression is a disease defining event in ACC that may have a pathological role. In addition, DLK1 serum levels, in combination with immunohistochemical expression in tumours, may provide a clinically useful novel biomarker for the diagnosis and monitoring of ACC.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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