Novel tumor markers are urgently needed to better stratify adrenocortical cancer (ACC) patients and improve therapies for this aggressive neoplasm.
To assess the diagnostic and prognostic value of the actin-bundling protein fascin-1 (FSCN1) in adrenocortical tumors.
A local series of 37 malignant/37 benign adrenocortical tumors at Careggi University Hospital and two independent validation ACC cohorts (Cochin, TCGA) from the European Network for the Study of Adrenal Tumors were studied.
FSCN1 expression was quantified by immunohistochemistry, Western Blot and quantitative RT-PCR analyses in ACC specimens; overall and disease-free survival associated with FSCN1 expression were assessed by Kaplan-Meier analysis and compared with that of Ki67 labelling index and tumor stage.
In spite of the low diagnostic power, in the Florence ACC series, FSCN1 immunohistochemical detection appeared as an independent prognostic factor, also refining results obtained with staging and Ki67 labelling index. The robust prognostic power of FSCN1 levels was further confirmed in two independent ACC cohorts. A positive correlation was found between FSCN1 and Steroidogenic Factor-1 (SF-1), with a significant higher expression of both factors in ACCs at advanced stages and with at least one of the three Weiss score parameters associated with invasiveness. Moreover, we demonstrated FSCN1 role in promoting cell invasion in a human ACC cell line only in the case of increased SF-1 dosage.
These findings show that FSCN1 is a novel independent prognostic marker in ACC and may serve as a potential therapeutic target to block tumor spread.
The Journal of clinical endocrinology and metabolism. 2018 Nov 23 [Epub ahead of print]
Giada Poli, Carmen Ruggiero, Giulia Cantini, Letizia Canu, Gianna Baroni, Roberta Armignacco, Anne Jouinot, Raffaella Santi, Tonino Ercolino, Bruno Ragazzon, Guillaume Assie, Massimo Mannelli, Gabriella Nesi, Enzo Lalli, Michaela Luconi
Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy., Université Côte d'Azur, Sophia Antipolis, Valbonne, France., Careggi University Hospital (AOUC), Florence, Italy., Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.