TGF-ß and CTGF are Mitogenic Output Mediators of Wnt/ß-Catenin Signaling in Desmoid Fibromatosis.

Desmoid fibromatosis is a locally aggressive clonal fibroblastic proliferation with high recurrence rates and no metastatic potential. Implicated molecular aberrations occur within the Wnt/ß-catenin pathway (APC and ß-catenin gene mutations). Transforming growth factor-ß (TGF-ß) and connective tissue growth factor (CTGF) are profibrotic growth factors, downstream from nuclear translocation of ß-catenin, that lead to increased fibrogenesis. CTGF (a downstream effector of TGF-ß) is a matricellular protein that modulates the activity of growth factors, adhesion molecules, integrins, and extracellular matrix thus playing a central role in tissue remodeling and fibrosis. Recently there has been growing interest in use of extracellular matrix inhibitors for treatment of various fibrogenic diseases. Desmoid fibromatosis samples (n=15) were evaluated for expression of ß-catenin, TGF-ß, and CTGF using immunohistochemistry on formalin paraffin-embedded material. A control group comprising scar tissue and adjacent normal skin (n=10) were simultaneously immunostained with above mentioned markers. Real-time polymerase chain reaction was performed on frozen specimens of desmoid fibromatosis (n=6) and normal skin (n=2). All 15 desmoid tumors were positive for ß-catenin (surrogate marker of Wnt/ß-catenin pathway dysregulation) which was negative in control normal skin and scar samples. TGF-ß and CTGF were negative in 9 of 10 normal skin controls. TGF-ß and CTGF were positive in all cases of scar tissue. All 15 cases of desmoid tumors were positive for TGF-ß and CTGF. The real-time polymerase chain reaction showed higher expression levels of TGF-ß and CTGF in desmoid fibromatosis compared with normal skin. The high constitutive expression of ß-catenin downstream effectors; TGF-ß, CTGF has the potential for enabling targeted therapy.

Diffuse malignant epithelioid mesothelioma in a background of benign multicystic peritoneal mesothelioma: a case report and review of the literature.

Peritoneal mesotheliomas are unusual entities with diverse origins and outcomes. Both benign and malignant variants exist. Benign multicystic peritoneal mesotheliomas (BMPMs), also known as multiple or multilocular peritoneal inclusion cysts, are extremely rare tumours arising from the peritoneal mesothelium covering the abdominal serous cavity. Even though these entities are considered benign tumours, BMPMs tend to recur after surgical resection, and in two cases have been reported to undergo malignant transformation. In contrast, diffuse malignant peritoneal mesotheliomas, while also quite rare, are the second most common form of malignant mesothelioma after the pleural variety with extremely high mortality and poor response to many treatments to date. We present a rare case of diffuse malignant peritoneal mesothelioma within a large component of a BMPM in a young man admitted to our service.