Search

Previous studies reported increased expression of the notch pathway-associated protein Musashi-1 in endometriosis. This case-control study investigates an association of the endometrial stem cell markers notch-1 and numb with endometriosis. Fifty-one endometriosis patients and 76 controls were recruited in the IVF unit and tertiary endometriosis referral centre of a university hospital. All subjects underwent transcervical endometrial biopsy and diagnostic laparoscopy. Expression of endometrial notch-1 and numb was assessed by immunostaining and correlated with clinical data. Association of stem-cell-marker expression with the presence of endometriosis was evaluated. Numb expression in the luminal epithelium was significantly higher in eutopic endometrium of endometriosis patients compared with controls (20.5% versus 16.5%, P = 0.033). Numb-positive single stromal cells were less frequent in endometrioma patients compared with other forms of endometriosis (0.3 versus 0.5 cells/visual field; P = 0.028). Notch-1 expression in endometrial glands was significantly higher in patients with deep infiltrating endometriosis compared with controls (39.1% versus 21.8%; P = 0.045). We conclude that stem cell markers notch-1 and numb of eutopic endometrium are associated with endometriosis and its clinical presentations, supporting the stem cell hypothesis of endometriosis. These findings could help develop promising research strategies applying endometrial stem cells as novel tools.

In KIT/PDGFRA wild-type gastrointestinal stromal tumors (wt-GISTs), BRAF mutations are regarded as alternative pathogenic events driving tumorigenesis. In our study, we aimed at analyzing a large cohort (n=444) of GISTs for BRAF mutations using molecular and immunohistochemical methods. More than 3000 GIST samples from caucasian patients were available in our GIST and Sarcoma Registry NRW. Of these, we selected 172 wt-GISTs to evaluate the frequency of BRAF mutations. Furthermore, 272 GISTs with a representative KIT and PDGFRA mutational status were selected. BRAF mutational status was evaluated by high-resolution melting analysis, Sanger sequencing, and VE1 immunohistochemistry. A BRAF mutation (p.V600E) was found in 7 cases (3.9%) of the wt-GIST cohort. In 2 cases, multiple synchronous tumors harbored the same somatic BRAF mutation. VE1 immunohistochemical staining had a sensitivity of 81.8% and a specificity of 97.5% to detect BRAF p.V600E mutations. Analyzing our cases and the cases reported in the literature (n=37), the percentage of intermediate and high-risk BRAF-mutated wt-GISTs (17/31; 54.8%) was comparable to that recorded for large GIST cohorts irrespective of the mutational status. BRAF mutations are rare events in wt-GISTs, and VE1 immunohistochemistry appears to be a valuable pre-screening tool for the detection of BRAF p.V600E mutations. BRAF mutations in GISTs do not seem to have a prognostic value per se. However, as BRAF inhibition represents a therapeutic option to control disease, we suggest the assessment of the BRAF mutational status, especially in the setting of advanced GIST disease.