Prognostic impact of tumor location and gene expression profile in sporadic desmoid tumor

• Published in: European journal of cancer (1990) Vol. 209; p. 114270
• Main Authors: Carrillo-García, Jaime, Hindi, Nadia, Conceicao, Magda, Sala, María Ángeles, Ugalde, Aitziber, López-Pousa, Antonio, Bagué, Silvia, Sevilla, Isabel, Vicioso, Luis, Ramos, Rafael, Martínez-Trufero, Javier, Gómez Mateo, Ma Carmen, Cruz, Josefina, Hernández-León, Carmen Nieves, Redondo, Andrés, Mendiola, Marta, García, Jerónimo Martínez, Hernández, José Emilio, Álvarez, Rosa, Agra, Carolina, de Juan-Ferré, Ana, Valverde, Claudia, Cano, Juana María, Sande, Luis Miguel de, Pérez-Fidalgo, José A., Lavernia, Javier, Marcilla, David, Gutiérrez, Antonio, Moura, David S., Martín-Broto, Javier
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.09.2024
• Subjects: CTNNB1 S45F; CTNNB1 T41A; Desmoid tumor; Relapse-free survival (RFS); Tumor location; Tumor location; CTNNB1 S45F; Relapse-free survival (RFS); CTNNB1 T41A; Desmoid tumor
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/j.ejca.2024.114270

Prognostic biomarkers remain necessary in sporadic desmoid tumor (DT) because the clinical course is unpredictable. DT location along with gene expression between thoracic and abdominal wall locations was analyzed. Sporadic DT patients (GEIS Registry) diagnosed between 1982 and 2018 who underwent upfront surgery were enrolled retrospectively in this study. The primary endpoint was relapse-free survival (RFS). Additionally, the gene expression profile was analyzed in DT localized in the thoracic or abdominal wall, harboring the most frequent CTNNB1 T41A mutation. From a total of 454 DT patients, 197 patients with sporadic DT were selected. The median age was 38.2 years (1.8–89.1) with a male/female distribution of 33.5/66.5. Most of them harbored the CTNNB1 T41A mutation (71.6 %), followed by S45F (17.8 %) and S45P (4.1 %). A significant worse median RFS was associated with males (p = 0.019), tumor size ≥ 6 cm (p = 0.001), extra-abdominal DT location (p < 0.001) and the presence of CTNNB1 S45F mutation (p = 0.013). In the multivariate analysis, extra-abdominal DT location, CTNNB1 S45F mutation and tumor size were independent prognostic biomarkers for worse RFS. DTs harboring the CTNNB1 T41A mutation showed overexpression of DUSP1, SOCS1, EGR1, FOS, LIF, MYC, SGK1, SLC2A3, and IER3, and underexpression of BMP4, PMS2, HOXA9, and WISP1 in thoracic versus abdominal wall locations. Sporadic DT location exhibits a different prognosis in terms of RFS favoring the abdominal wall compared to extra-abdominal sites. A differential gene expression profile under the same CTNNB1 T41A mutation is observed in the abdominal wall versus the thoracic wall, mainly affecting the Wnt/β-catenin, TGFβ, IFN, and TNF pathways. •Location, CTNNB1 S45F and tumor size are prognostic biomarkers in desmoid tumor (DT) patients.•Location of DTs harboring the CTNNB1 T41A mutation is a prognostic biomarker.•Gene expression of DTs harboring CTNNB1 T41A changes between locations in the thoracic and abdominal walls.•These changes mainly affect the Wnt/β-catenin, TGFβ, IFN and TNF signaling pathways.