The insulin-like growth factor 2 (IGF2) promotes cell growth by overactivating the IGF system in an autocrine loop in adrenocortical carcinomas (ACCs). The cytoskeleton protein filamin A (FLNA) acts as a repressor of IGF2 mitogenic signalling in ACC cells. The aims of this study were to test FLNA expression by immunohistochemistry in 119 ACCs and 26 adrenocortical adenomas (ACAs) and to evaluate its relationship with clinicopathological features and outcome in ACCs. We found that 71.4% of ACCs did not express FLNA, whereas FLNA absence was a rare event in ACAs (15.4%, p < 0.001 vs. ACCs). In addition, the expression of FLNA was associated with a less aggressive tumour behaviour in ACCs. Indeed, the subgroup of ACCs with high FLNA showed a lower ENSAT stage, Weiss score, and S-GRAS score compared to ACCs with low FLNA expression (p < 0.05). Moreover, patients with high FLNA had a longer overall survival than those with low FLNA (p < 0.05). In conclusion, our data suggest that FLNA may represent a "protective" factor in ACCs, and the integration of FLNA immunohistochemical expression in ACC tissues along with other clinical and molecular markers could be helpful to improve diagnostic accuracy and prognosis prediction in ACCs.

High Filamin a Expression in Adrenocortical Carcinomas Is Associated with a Favourable Tumour Behaviour: A European Multicentric Study / R. Catalano, B. Altieri, A. Angelousi, M. Arosio, F. Bravi, L. Canu, G.A. Croci, M. Detomas, E. Esposito, E. Ferrante, S. Ferrero, C.T. Fuss, G. Kaltsas, O. Kimpel, L. Landwehr, M. Luconi, V. Morelli, G. Nesi, E. Nozza, S. Sbiera, A.L. Serban, C.L. Ronchi, G. Mantovani, E. Peverelli. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 24:23(2023 Dec), pp. 1-13. [10.3390/ijms242316573]

High Filamin a Expression in Adrenocortical Carcinomas Is Associated with a Favourable Tumour Behaviour: A European Multicentric Study

R. Catalano
Primo
;
F. Bravi;G.A. Croci;S. Ferrero;E. Nozza;G. Mantovani
;
E. Peverelli
Ultimo
2023

Abstract

The insulin-like growth factor 2 (IGF2) promotes cell growth by overactivating the IGF system in an autocrine loop in adrenocortical carcinomas (ACCs). The cytoskeleton protein filamin A (FLNA) acts as a repressor of IGF2 mitogenic signalling in ACC cells. The aims of this study were to test FLNA expression by immunohistochemistry in 119 ACCs and 26 adrenocortical adenomas (ACAs) and to evaluate its relationship with clinicopathological features and outcome in ACCs. We found that 71.4% of ACCs did not express FLNA, whereas FLNA absence was a rare event in ACAs (15.4%, p < 0.001 vs. ACCs). In addition, the expression of FLNA was associated with a less aggressive tumour behaviour in ACCs. Indeed, the subgroup of ACCs with high FLNA showed a lower ENSAT stage, Weiss score, and S-GRAS score compared to ACCs with low FLNA expression (p < 0.05). Moreover, patients with high FLNA had a longer overall survival than those with low FLNA (p < 0.05). In conclusion, our data suggest that FLNA may represent a "protective" factor in ACCs, and the integration of FLNA immunohistochemical expression in ACC tissues along with other clinical and molecular markers could be helpful to improve diagnostic accuracy and prognosis prediction in ACCs.
ACC prognostic factor; IGF2; adrenocortical carcinoma; filamin A; molecular marker
Settore MED/08 - Anatomia Patologica
Settore MED/13 - Endocrinologia
Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio
   Dissecting molecular mechanisms regulating insulin-like growth factor (IGF) system in adrenocortical carcinomas (1° anno)
   FONDAZIONE AIRC PER LA RICERCA SUL CANCRO ETS
   AIRC IG 2021 ID 25920

   IN Search of early clinical and molecular Predictors of diagnosis and treatment response In patients with Rare Endocrine disorders: retrospective analysis on large healthcare database network and translational cohort studies (the INSPIRE project)
   the INSPIRE project
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
   2017N8CK4K_003
dic-2023
21-nov-2023
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1022671
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