Wnt/ß-catenin-C-kit axis may play a role in adenoid cystic carcinoma prognostication.

Adenoid cystic carcinoma (ACC) is one of the most common malignant salivary gland tumors. ACC is composed of myoepithelial and epithelial neoplastic cells which grow slowly and have a tendency for neural invasion. The long term prognosis is still relatively poor. Although several gene abnormalities, such as fusions involving MYB or MYBL1 oncogenes and the transcription factor gene NFIB, and overexpression of KIT have been reported in ACC, their precise functions in the pathogenesis of ACC remain unclear. We recently demonstrated that the elevated expression of Semaphorin 3A (SEMA3A), specifically expressed in myoepithelial neoplastic cells, might function as a novel oncogene-related molecule to enhance cell proliferation through activated AKT signaling in 9/10 (90%) ACC cases. In the current study, the patient with ACC whose tumor was negative for SEMA3A in the previous study, revisited our hospital with late metastasis of ACC to the cervical lymph node eight years after surgical resection of the primary tumor. We characterized this recurrent ACC, and compared it with the primary ACC using immunohistochemical methods. In the recurrent ACC, the duct lining epithelial cells, not myoepithelial neoplastic cells, showed an elevated Ki-67 index and increased cell membrane expression of C-kit, along with the expression of phosphorylated ERK. Late metastasis ACC specimens were not positive for ß-catenin and lymphocyte enhancer binding factor 1 (LEF1), which were detected in the nuclei of perineural infiltrating cells in primary ACC cells. In addition, experiments with the GSK-3 inhibitor revealed that ß-catenin pathway suppressed not only KIT expression but also proliferation of ACC cells. Moreover, stem cell factor (SCF; also known as KIT ligand, KITL) induced ERK activation in ACC cells. These results suggest that inactivation of Wnt/ß-catenin signaling may promote C-kit-ERK signaling and cell proliferation of in metastatic ACC.

The effect of anterior support screw (AS2) in unstable femoral trochanteric fractures: A multicenter randomized controlled trial.

OBJECTIVES: This study was conducted to verify the effectiveness of Anterior Support Screw (AS2) for unstable femoral trochanteric fractures. DESIGN: A multicenter, prospective, randomized controlled trial SETTING: This study was conducted across 15 academic medical centers in Japan PATIENTS/PARTICIPANTS: We enrolled 240 cases of femoral trochanteric fractures with posterior crushing and intramedullary displacement of proximal bone fragments across 15 institutions in Japan. INTERVENTION: All patients were subjected to a reduction in which the anterior cortex was brought into contact. The patients were randomly assigned to the anterior support screw group (AS2 group) and the non-screw group (control group). MAIN OUTCOME MEASUREMENTS: Two computed-tomography (CT) scans were taken immediately after surgery and early postoperative period (day 14-21) to investigate the reduction loss rate of the anterior cortex and sliding distances in the early postoperative period. RESULTS: The reduction loss rate was 4.5 % in the AS2 group and 16.8 % in the control group, indicating a significantly lower reduction loss rate in the AS2 group (p = 0.003). The average sliding distance was 1.8 mm in the AS2 group and 2.8 mm in the control group, indicating a significantly shorter sliding distance in the AS2 group (p < 0.0001). CONCLUSION: Adding a screw in front of the intramedullary nail significantly reduces reduction loss, and maintains anterior bony contact. This study also showed that these screws suppress the sliding distance during the postoperative period. LEVEL OF EVIDENCE: Therapeutic Level I.