Fascin-1 Is a Novel Prognostic Biomarker Associated With Tumor Invasiveness in Adrenocortical Carcinoma

Giada Poli (1) , Carmen Ruggiero (2, 3) , Giulia Cantini (1) , Letizia Canu (1, 4) , Gianna Baroni (1, 4) , Roberta Armignacco (1, 5) , Anne Jouinot (5, 6) , Raffaella Santi (1, 4) , Tonino Ercolino (4) , Bruno Ragazzon (5) , Guillaume Assie (5, 6) , Massimo Mannelli (1, 4) , Gabriella Nesi (1, 4) , Enzo Lalli (2) , Michaela Luconi (1, 4)

1 UniFI - Università degli Studi di Firenze = University of Florence = Université de Florence
2 IPMC - Institut de pharmacologie moléculaire et cellulaire
3 LIA Neogenex - Laboratoire International Associé "Neogenex"
4 AOUC - Azienda Ospedaliero Universitaria Careggi [Firenze] = Careggi University Hospital [Florence, Italy]
5 IC UM3 (UMR 8104 / U1016) - Institut Cochin
6 Hôpital Cochin [AP-HP]

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 in ACC specimens; overall and disease-free survival associated with FSCN1 expression were assessed by Kaplan-Meier analysis and compared with that of Ki67 labeling index and tumor stage. Results Despite 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 labeling 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 substantially 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.

Mots clés: ACC; cancer invasion; prognostic value; overall survival; recurrence

Domaines: Sciences du Vivant [q-bio]

Giada Poli, Carmen Ruggiero, Giulia Cantini, Letizia Canu, Gianna Baroni, et al.. Fascin-1 Is a Novel Prognostic Biomarker Associated With Tumor Invasiveness in Adrenocortical Carcinoma. Journal of Clinical Endocrinology and Metabolism, 2019, 104 (5), pp.1712-1724. ⟨10.1210/jc.2018-01717⟩. ⟨hal-03538480⟩