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

Giada Poli,Gianna Baroni,Anne Jouinot,Tonino Ercolino,Gabriella Nesi,Bruno Ragazzon,Massimo Mannelli,Carmen Ruggiero,Enzo Lalli,Giulia Cantini,Michaela Luconi,Guillaume Assie,Raffaella Santi,Roberta Armignacco,Letizia Canu

doi:10.1210/jc.2018-01717

Abstract

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 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. 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. 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.

Highlights

Adrenocortical cancer (ACC) is a rare endocrine tumor with poor prognosis, when metastatic at diagnosis
FSCN1 expression was evaluated by immunohistochemistry and Western blotting in samples from a series of n=37 adrenocortical cancer (ACC) and n=37 adrenocortical tumours (ACA) diagnosed and operated at Careggi University Hospital
Clinico-pathological characteristics are described in Table 1 (ACCs) and Table 2 (ACAs)

Summary

Introduction

Adrenocortical cancer (ACC) is a rare endocrine tumor with poor prognosis, when metastatic at diagnosis. It lacks selective and efficacious therapies, which currently consist of surgical resection (R0) and administration of the adrenolytic drug mitotane [1] in association with cytotoxic agents in advanced stages [2]. Few studies have searched for protein markers capable of discriminating between benign forms of adrenocortical tumours (ACA) and ACC, and predicting tumor progression [5]. A recent proteomic study [6] identified Fascin-1 (FSCN1) as a potential malignancy marker by a twodimensional-differential-in-gel-electrophoretic (2D-DIGE) approach performed in ACC versus normal adrenals. FSCN1 is an actin-bundling protein involved in formation of filopodia and invadopodia [7,8]

Methods

Results

Conclusion