Prognostic Value of CTNNB1 Gene Mutation in Primary Sporadic Aggressive Fibromatosis

• Published in: Annals of surgical oncology Vol. 22; no. 5; pp. 1464 - 1470
• Main Authors: van Broekhoven, Danique L. M., Verhoef, Cornelis, Grünhagen, Dirk J., van Gorp, Joost M. H. H., den Bakker, Michael A., Hinrichs, John W. J., de Voijs, Carmen M. A., van Dalen, Thijs
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.05.2015; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; beta Catenin - genetics; Bone and Soft Tissue Sarcomas; Child; Child, Preschool; Female; Fibromatosis, Aggressive - genetics; Fibromatosis, Aggressive - mortality; Fibromatosis, Aggressive - pathology; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation - genetics; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - mortality; Neoplasm Staging; Oncology; Prognosis; Surgery; Surgical Oncology; Survival Rate; Young Adult; Complete Tumor Resection; T41A Mutation; Clinicopathologic Factor; CTNNB1 Mutation; Aggressive Fibromatosis
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-014-4156-x

Background Aggressive fibromatosis (AF) comprises tumors with a varying biological behavior. Genetic tumor characteristics may be predictive of recurrence; hence, the prognostic value of three specific mutations on the CTNNB1 gene was evaluated in relation to known clinicopathologic risk factors in patients with primary, sporadic AF. Methods In a multi-institutional retrospective cohort study of patients with primary extra-abdominal and abdominal wall AF who underwent surgical treatment, the original pathology specimens were reviewed for the presence of a T41A, S45F, and 45P mutations on the CTNNB1 gene. For these mutations, the risk of recurrence was analyzed by the Kaplan–Meier method with log-rank test. Univariable and multivariable Cox regression was performed to calculate hazard ratios. Results A total of 101 patients were analyzed. During a median follow-up of 41 months, 17 recurrences were detected; the cumulative 5-year recurrence rate was 22.8 %. A specific CTNNB1 mutation was found in 76 patients, with the majority of patients having a T41A mutation ( n  = 49). CTNNB1 mutations were associated with the risk of recurrence: the presence of a S45F mutation was associated with a 5-year cumulative risk of recurrence of 63.8 % ( P  < 0.001). Multivariable analysis showed that young age and S45F mutation were independent risk factors ( P  = 0.011 and P  < 0.001). Conclusions The presence of specific CTNNB1 mutations was predictive for recurrence in patients after surgical treatment for primary, sporadic extra-abdominal and abdominal AF. A S45F mutation increased the risk of recurrence significantly.