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J Clin Endocrinol Metab. 2018 Nov 23. doi: 10.1210/jc.2018-01717. [Epub ahead of print]

Fascin-1 is a Novel Prognostic Biomarker Associated with Tumor Invasiveness in Adrenocortical Carcinoma.

Author information

1
Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
2
Université Côte d'Azur, Sophia Antipolis, Valbonne, France.
3
CNRS UMR7275, Sophia Antipolis, Valbonne, France.
4
NEOGENEX CNRS International Associated Laboratory, Sophia Antipolis, Valbonne, France.
5
Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, Valbonne, France.
6
Careggi University Hospital (AOUC), Florence, Italy.
7
Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
8
Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
9
Department of Endocrinology Cochin Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.1.
10
Reference Center for Rare Adrenal Diseases Reference Center for Rare Adrenal Cancer Network COMETE, Hôpital Cochin, Assistance Publique - Hôpitaux de Paris, Paris, France.

Abstract

CONTEXT:

Novel tumor markers are urgently needed to better stratify adrenocortical cancer (ACC) patients and improve therapies for this aggressive neoplasm.

OBJECTIVE:

To assess the diagnostic and prognostic value of the actin-bundling protein fascin-1 (FSCN1) in adrenocortical tumors.

DESIGN, SETTING AND PARTICIPANTS:

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.

MAIN OUTCOME MEASURES:

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.

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
30476173
DOI:
10.1210/jc.2018-01717

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