Beta-catenin S45F mutation results in apoptotic resistance

Wnt/beta-catenin signaling is one of the key cascades regulating embryogenesis and tissue homeostasis; it has also been intimately associated with carcinogenesis. This pathway is deregulated in several tumors, including colorectal cancer, breast cancer, and desmoid tumors. It has been shown that CTNNB1 exon 3 mutations are associated with an aggressive phenotype in several of these tumor types and may be associated with therapeutic tolerance. Desmoid tumors typically have a stable genome with beta-catenin mutations as a main feature, making these tumors an ideal model to study the changes associated with different types of beta-catenin mutations. Here, we show that the apoptosis mechanism is deregulated in beta-catenin S45F mutants, resulting in decreased induction of apoptosis in these cells. Our findings also demonstrate that RUNX3 plays a pivotal role in the inhibition of apoptosis found in the beta-catenin S45F mutants. Restoration of RUNX3 overcomes this inhibition in the S45F mutants, highlighting it as a potential therapeutic target for malignancies harboring this specific CTNNB1 mutation. While the regulatory effect of RUNX3 in beta-catenin is already known, our results suggest the possibility of a feedback loop involving these two genes, with the CTNNB1 S45F mutation downregulating expression of RUNX3, thus providing additional possible novel therapeutic targets for tumors having deregulated Wnt/beta-catenin signaling induced by this mutation.

The abdominal desmoid tumor shows invasive development and high local recurrence rate. The primary treatment method is complete removal of the tumor because of the high recurrence rate; however, the problem for the surgeon is the reconstruction of the abdominal wall after resection of the abdominal desmoid tumor. A 63-year-old man underwent open drainage and ileostomy for the perforation of ileocecal tumor. After 3 months, he underwent right hemicolectomy and ileostomy closure. Pathological examination revealed no malignancy, and the ileocecal tumor showed the presence of abscess. He noticed a palpable mass in the left abdomen. Enhanced abdominal computed tomography (CT) revealed a large abdominal incisional hernia and an enhanced mass of 40 mm in the left rectus muscle. Needle biopsy was performed and the diagnosis was desmoid tumor. He underwent resection of the desmoid tumor and repair of hernia. We performed wide local resection, with a 2-cm surgical margin. The hernia was repaired by simple closure, and the defect in the left abdomen was repaired with reconstruction using the fascia lata patch through plastic surgery. The patient has not shown recurrence of incisional hernia or desmoid tumor 22 months after surgery.

We present the case of a patient with an inflammatory bowel disease to whom a pelvic desmoid tumor is discovered during an infertility study.

This study was undertaken to clarify the risk factors, including the mutation status of CTNNB1, for the local recurrence after surgery of the rare disease, desmoid-type fibromatosis. It was designed as a multi-institutional joint research project with seven major centers in Japan participating. Of 196 cases with specimens and medical records collected from the 7 institutions, 88 surgically treated ones were analyzed regarding clinicopathological prognostic factors including CTNNB1 mutation status. Excluding R2 cases (n=3), 5-year local recurrence free survival (LRFS) was 52.9%. No case had received pre- or post-operative radiotherapy. Univariate analysis revealed that extremity location (P<0.001) and larger size (?8cm, P=0.036) were significant adverse risk factors for LRFS. Multivariate analysis demonstrated that extremity location (P<0.001) was a significantly adverse factor in addition to recurrent tumor (P=0.041), S45F mutation (P=0.028), and R1 surgical margin (P=0.039). Pre-operative drug treatment including NSAIDs did not reduce the incidence of local recurrence (P=0.199). This is the first study to analyze the factors correlating with outcomes of surgical treatment including CTNNB1 mutation status in a relatively large number of cases from an Asian country. Tumor location was found to be the most influential prognostic factor for local recurrence, similar to the results from Western countries. The development of more sensitive method(s) for determination of CTNNB1 mutation is a priority for future study.

In this study, we aimed to present our surgical approach, tumor characteristics, clinical presentation and long-term follow-up results in cases of primary mesenteric fibromatosis. The data collected from 11 patients who underwent surgery due to primary mesenteric fibromatosis in our clinic between 2010 and 2019 were analyzed retrospectively. Abdominal pain, abdominal distention, and two patients (18.2%) were operated on with a diagnosis of acute abdomen in the emergency setting due to mechanical bowel obstruction in one patient. There were 11 patients in our study. Six patients were female and 5 were male. The mean age was 44.2ñ15.8 years. Abdominal mass was detected in 5 patients (45.5%) who had complaints of mechanical bowel obstruction such as nausea and vomiting and gastrointestinal perforation in other patient. Mesenteric mass was detected in 3 patients (27.3%) with vague abdominal pain. One patient (9.1%) presented with abdominal pain and swelling of the right leg. After a mean follow-up period of 43.4ñ28.4 months, only 1 patient (9.1%) had recurrence and required reoperation approximately 80 months after the first operation. One patient (9.1%) died of anastomotic leakage and sepsis in the first 30 days postoperatively, and other patient (9.1%) died of other reasons 1 year later postoperatively. Although mesenteric fibromatosis is a benign tumor pathologically, the main principle in the treatment of this tumor which is clinically aggressive and has high recurrence rate is wide surgical resection. Mesenteric fibromatoses have a varied clinical presentation. Radiological imaging methods helps diagnosis and planning the surgical treatment. Immunohistochemical characteristics confirms the diagnosis and differentiates from other similar tumors.

Here we report a case of huge mesenteric fibromatosis who complained a paroxysmal epigastric pain, and CT scan showed a huge mass, pneumoperitoneum and ascites. An urgent laparotomy showed an intro-abdominal mass and perforation locating at the jejunum. Postoperative histology confirmed it to be mesenteric fibromatosis. With one-year follow-up, the patient had no recurrence. We wish to share our treating experience of this interesting case because it did not belong to a typical type but presenting with acute diffuse peritonitis, and total resection and R0 margin is a key to treat acute case.