Giada Poli1, Carmen Ruggiero2,3,4,5, Giulia Cantini1, Letizia Canu1,6, Gianna Baroni6,7, Roberta Armignacco1,8, Anne Jouinot8,9, Raffaella Santi6,7, Tonino Ercolino6, Bruno Ragazzon8, Guillaume Assie8,9,10, Massimo Mannelli1,6, Gabriella Nesi6,7, Enzo Lalli2,3,4,5, Michaela Luconi1,6. 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. 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 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.
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.
Authors: Barbara Kiesewetter; Philipp Riss; Christian Scheuba; Peter Mazal; Elisabeth Kretschmer-Chott; Alexander Haug; Markus Raderer Journal: Ther Adv Med Oncol Date: 2021-08-31 Impact factor: 5.485
Authors: Peter M van Koetsveld; Sara G Creemers; Fadime Dogan; Gaston J H Franssen; Wouter W de Herder; Richard A Feelders; Leo J Hofland Journal: J Clin Endocrinol Metab Date: 2020-02-01 Impact factor: 5.958