TY - JOUR
T1 - High filamin A expression in adrenocortical carcinomas is associated with a favourable tumor behaviour
T2 - a European multicentric study
AU - Catalano, Rosa
AU - Altieri, Barbara
AU - Angelousi, Anna
AU - Arosio, Maura
AU - Bravi, Francesca
AU - Canu, Letizia
AU - Croci, Giorgio
AU - Detomas, Mario
AU - Esposito, Emanuela
AU - Ferrante, Emanuele
AU - Ferrero, Stefano
AU - Fuss, Carmina
AU - Kaltsas, Gregory
AU - Kimpel, Otilia
AU - Landwehr, Laura-Sophie
AU - Luconi, Michaela
AU - Morelli, Valentina
AU - Nesi, Gabriella
AU - Nozza, Emma
AU - Sbiera, Silviu
AU - Serban, Andreea L.
AU - Ronchi, Cristina L.
AU - Mantovani, Giovanna
AU - Peverelli, Erika
N1 - Funding:
This research was funded by an AIRC (Associazione Italiana Ricerca Cancro) grant to E.P. (IG 2021-25920), by a Progetti di Ricerca di Interesse Nazionale (PRIN) grant to E.P. (2017N8CK4K), and by Ricerca Corrente Funds from the Italian Ministry of Health to Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico.
PY - 2023/11/21
Y1 - 2023/11/21
N2 - 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.
AB - 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.
KW - filamin A
KW - IGF2
KW - adrenocortical carcinoma
KW - molecular marker
KW - ACC prognostic factor
U2 - 10.3390/ijms242316573
DO - 10.3390/ijms242316573
M3 - Article
SN - 1661-6596
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 23
M1 - 16573
ER -