Prognostic value of CTNNB1 gene mutation in primary sporadic aggressive fibromatosis

Abstract

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.