CTNNB1 Mutational Profile with Clinico-pathological Parameters of Indian Patients with Desmoid-Type Fibromatosis: A Retrospective Study

Desmoid-type fibromatosis (DTF) is a rare mesenchymal tumor characterized by high local recurrence and no metastatic potential, with sporadic cases often linked to CTNNB1 gene mutations. While global studies have detailed the frequency and prognostic significance of these mutations, there remains a significant lack of large-scale mutational profiling data from the Indian subcontinent. This study aims to address this knowledge gap by providing the first molecular description of CTNNB1 mutational subtypes in an Indian DTF patient population. The aim of the study is to characterize the CTNNB1 exon-3 mutational profile in Indian patients with DTF and to evaluate its association with key clinicopathological features and treatment outcomes. This retrospective analysis included formalin-fixed paraffin-embedded (FFPE) tissue blocks from 38 histopathologically confirmed DTF patients treated at a single tertiary center in India between January 2021 to April 2025. DNA was extracted from each of these patients, and exon-3 of the CTNNB1 gene was amplified using polymerase chain reaction, followed by bidirectional sequencing for mutation identification. Histopathological diagnoses were independently validated by two sarcoma pathology experts. Clinical data, including demographics, tumor characteristics, and treatment outcomes, were collected from medical records. The cohort included 38 patients (24 women, 14 men; median age 29.5 years, range 7–59). CTNNB1 mutations were present in 23 patients (60.5%). Extremities (36.8%) and the abdomen (34.2%) were the most common tumor sites, with a median baseline tumor diameter of 7.95 cm. Among mutation-positive cases, T41A was most frequent (60.9%), followed by S45F (30.4%) and S45P (8.7%). Fifteen patients (39.5%) had CTNNB1 wild-type tumors. Surgery was the most common initial treatment (15/38). Recurrence occurred in 17 of 29 surgically treated patients (58.6%), including 5 of 7 (71.4%) with S45F mutations. In later treatment lines, active surveillance (50%) and sorafenib (42.1%) predominated. Overall, 26 patients (68.4%) achieved disease control. This study offers initial insights into CTNNB1 mutations in Indian DTF patients, revealing a higher frequency of the wild-type gene compared with international data. This finding suggests potential regional differences in disease characteristics. Therefore, further extensive, multi-center studies with long-term follow-up are essential to fully understand DTF in the Indian population, which will be crucial for developing more precise diagnostic methods and effective treatment strategies tailored to this specific demographic.