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The Desmoid Tumor Research Foundation

August 2024

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

Author Information

Jaime Carrillo-García 1, Nadia Hindi 2, Magda Conceicao 3, María Ángeles Sala 4, Aitziber Ugalde 5, Antonio López-Pousa 6, Silvia Bagué 7, Isabel Sevilla 8, Luis Vicioso 9, Rafael Ramos 10, Javier Martínez-Trufero 11, Ma Carmen Gómez Mateo 12, Josefina Cruz 13, Carmen Nieves Hernández-León 14, Andrés Redondo 15, Marta Mendiola 16, Jerónimo Martínez García 17, José Emilio Hernández 18, Rosa Álvarez 19, Carolina Agra 20, Ana de Juan-Ferré 21, Claudia Valverde 22, Juana María Cano 23, Luis Miguel de Sande 24, José A Pérez-Fidalgo 25, Javier Lavernia 26, David Marcilla 27, Antonio Gutiérrez 28, David S Moura 29, Javier Martín-Broto 30

1Health Research Institute Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, Spain; Medical Oncology Department, University Hospital General de Villalba, Madrid, Spain. Electronic address: jcarrillo@atbsarc.org. 2Health Research Institute Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, Spain; Medical Oncology Department, University Hospital General de Villalba, Madrid, Spain; Medical Oncology Department, University Hospital Fundación Jiménez Díaz, Madrid, Spain. Electronic address: nhindi@atbsarc.org. 3University Hospital Son Espases, Palma, Spain. Electronic address: magdacristina.daconceicao@ssib.es. 4Medical Oncology Department, Basurto University Hospital, Bilbao, Spain. Electronic address: MARIAANGELES.SALAGONZALEZ@osakidetza.eus. 5Pathology Department, Basurto University Hospital, Bilbao, Spain. Electronic address: AITZIBER.UGALDEOLANO@osakidetza.eus. 6Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Electronic address: ALopezP@santpau.cat. 7Pathology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Electronic address: sbaguer@santpau.cat. 8Clinical and Translational Research in Cancer/Biomedical Reseach Institute of Malaga (IBIMA), University Hospitals Regional and Virgen de la Victoria, Malaga, Spain. Electronic address: isevilla02@yahoo.es. 9Pathology Department, University Hospital Virgen de la Victoria, IBIMA-Plataforma Bionand, Malaga, Spain. Electronic address: vicioso@uma.es. 10Pathology Department, University Hospital Son Espases, Palma, Spain. Electronic address: rafaelf.ramos@quironsalud.es. 11Medical Oncology Department, University Hospital Miguel Servet, Zaragoza, Spain. Electronic address: jmtrufero@seom.org. 12Pathology Department, University Hospital Miguel Servet, Zaragoza, Spain. Electronic address: mcgomezmateo@hotmail.com. 13Medical Oncology Department, University Hospital of Canarias, Santa Cruz de Tenerife, Spain. Electronic address: jcruzjurado@gmail.com. 14Pathology Department, University Hospital of Canarias, Santa Cruz de Tenerife, Spain. Electronic address: nievleon34@gmail.com. 15Medical Oncology Department, University Hospital La Paz-IdiPAZ, Madrid, Spain. Electronic address: andres.redondos@uam.es. 16Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain; Hospital La Paz Institute for Health Research - IDIPAZ, La Paz University Hospital, Madrid, Spain. Electronic address: marta.mendiola@salud.madrid.org. 17Oncology Department, University Hospital Virgen de la Arrixaca, Murcia, Spain. Electronic address: jeronimo@seom.org. 18Pathology Department, University Hospital Virgen de la Arrixaca, Murcia, Spain. Electronic address: joseemilio99@yahoo.es. 19Medical Oncology Department, University Hospital Gregorio Marañón, Madrid, Spain. Electronic address: rosa.alvarez.al@gmail.com. 20Pathology Department, University Hospital Gregorio Marañón, Madrid, Spain. Electronic address: caroagra@gmail.com. 21Medical Oncology Department, University Hospital Marqués de Valdecilla, IDIVAL, Santander, Spain. Electronic address: anade.juan@scsalud.es. 22Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain. Electronic address: cvalverde@vhio.net. 23Medical Oncology Department, University Hospital of Ciudad Real, Ciudad Real, Spain. Electronic address: juanamariacano@gmail.com. 24Medical Oncology Department, University Hospital of León, León, Spain. Electronic address: lmgdesande@gmail.com. 25Hematology and Medical Oncology Department, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain. Electronic address: apfidalgo@msn.com. 26Oncology Department, Instituto Valenciano de Oncología, Valencia, Spain. Electronic address: javilavernia@gmail.com. 27Pathology Department, University Hospital Virgen del Rocío, Sevilla, Spain. Electronic address: david.marcilla.sspa@juntadeandalucia.es. 28Department of Haematology, University Hospital Son Espases, IdISBa, Palma, Spain. Electronic address: antoniom.gutierrez@ssib.es. 29Health Research Institute Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, Spain; Medical Oncology Department, University Hospital General de Villalba, Madrid, Spain. Electronic address: dmoura@atbsarc.org. 30Health Research Institute Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, Spain; Medical Oncology Department, University Hospital General de Villalba, Madrid, Spain; Medical Oncology Department, University Hospital Fundación Jiménez Díaz, Madrid, Spain. Electronic address: jmartin@atbsarc.org.

Publication

Eur J Cancer

Summary

Purpose: 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. Method: 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. Results: 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. Conclusion: 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.

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