Molecular-genetic landscape of abdominal and retroperitoneal desmoid fibromatosis: a retrospective study

Abstract

Background. Desmoid fibromatosis (DF) is a rare mesenchymal tumor with invasive growth, a high relapse rate, and low incidence (24 cases per 1 million people per year). Given the small number of patients with DF and, as a result, the lack of knowledge of this disease, the search for molecular predictors of the disease course and the individualization of treatment and prevention is relevant. Aim. To study tumor cells' molecular genetic and immunohistochemical profile and determine their clinical significance in patients with abdominal and retroperitoneal DF. Materials and methods. A comprehensive analysis of clinical and laboratory data of 31 patients with abdominal and retroperitoneal DF, a molecular genetic and morphological study of tumor samples was performed, including next-generation sequencing (NGS) using the Onconetix oncology panel and an immunohistochemical study using antibodies to -catenin and estrogen and progesterone receptors. Results. NGS testing showed somatic mutations in 28 (90%) of the 31 tumor samples. Somatic mutations in the CTNNB1 gene were detected in 26 (84%) tumor samples: 21 (68%) patients had c.121AG (p.Thr41Ala, rs121913412), 3 (10%) patients had c.134CT (p.Ser45Phe, rs121913409), 1 (3%) patient had c.133TC (p.Ser45Pro, rs121913407), and 1 (3%) patient had c.122CT (p.Thr41Ile, rs121913413). Two (6%) patients had mutations in the APC gene: c.4381GT (p.Glu1461Ter, COSM30779) and c.4634CA (p.Ser1545Ter, rs863225356). In 3 (9%) patients, no mutations were detected in the studied genes. The immunohistochemical study showed the expression of -catenin in the cytoplasm and nuclei of tumor cells in 16 (51.6%) samples. Nuclear expression of estrogen and progesterone receptors was detected in 6 (19%) and 1 (3.2%) samples, respectively. Of 10 patients with established relapses, sequencing (NGS) showed a c.121AG mutation (p.Thr41Ala, rs121913412) in 7; 1 patient had a c.134CT mutation (p.Ser45Phe, rs121913409), and 2 patients had no mutations in tumor samples. Conclusion. The combination of factors such as the retroperitoneal DF, the presence of the c.121AG mutation (p.Thr41Ala, rs121913412) in the CTNNB1 gene, female gender, and young age, can warrant assigning the patient to the group with an unfavorable DF prognosis.

Keywords

• desmoid fibromatosis
• retroperitoneal
• β-catenin
• next-generation sequencing