Myxoid Spindle Cell Sarcoma With LMNA-NTRK Fusion: Expanding the Morphologic Spectrum of NTRK-Rearranged Tumors.

Neurotrophic tyrosine receptor kinase (NTRK)-rearranged spindle cell neoplasm is a recently described soft tissue tumor entity that occurs predominantly in children and young adults. The diagnosis of this tumor is difficult due to the nonspecific and highly variable morphology, yet it is of clinical relevance because of the availability of highly effective TRK inhibitors. In this article, we report the case of a 40-year-old female who presented with a mass in the left calf. Histologic examination revealed a low-grade sarcoma consisting of monomorphic spindle cells accompanied by abundant myxoid stroma, a feature that had not been emphasized in the reported cases of NTRK-rearranged tumors. The tumor cells expressed CD34 and S100 but not SOX10, and they showed positive staining for pan-TRK. Next-generation sequencing showed the presence of LMNA-NTRK1 fusion. The patient developed several episodes of lung metastases that eventually became unresectable. TRK inhibitor was given that led to near-complete resolution of the tumors.

ADAM9 Mediates Triple-Negative Breast Cancer Progression via AKT/NF-κB Pathway.

Upregulation of a disintegrin and metalloprotease 9 (ADAM9) is correlated with progression of cancers, such as prostate, bladder, and pancreatic cancers. However, its role in triple-negative breast cancer (TNBC) is still unclear. Our study aimed to investigate whether ADAM9 is upregulated and promoted the aggressiveness in TNBC. Breast cancer cell lines and patient specimens were used to evaluate the ADAM9 expression by western blotting and immunohistochemistry staining, respectively. Compared with the non-TNBC, ADAM9 expression was significantly increased in TNBC cells and TNBC patient specimens. Based on the data acquired from public databases, the correlation between ADAM9 expression and breast cancer patient survival was analyzed by Kaplan-Meier method. It was shown that ADAM9 overexpression was significantly correlated with poorer survival in patients with TNBC. Furthermore, ADAM9 in TNBC cells was knocked down by small interference RNA and then studied by the MTT/colony formation assay, wound healing assay and transwell invasion assay on the cell proliferation, migration, and invasion, respectively. We found that inhibiting ADAM9 expression suppressed TNBC cell proliferation, migration, and invasion by lowering the activation of AKT/NF-κB pathway. Our results demonstrated that ADAM9 is an important molecule in mediating TNBC aggressiveness and may be a potential useful therapeutic target in TNBC treatment.