Myxoinflammatory fibroblastic sarcoma (MIFS) is a low-grade malignant neoplasm for which limited genetic information, including a t(1;10)(p22;q24) and amplification of chromosome 3 material, is available. To further characterize these aberrations, we have investigated eight soft tissue sarcomas diagnosed as MIFS, haemosiderotic fibrolipomatous tumour (HFT), myxoid spindle cell/pleomorphic sarcoma with MIFS features, and inflammatory malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma with prominent inflammation (IMFH) harbouring a t(1;10) or variants thereof and/or ring chromosomes with possible involvement of chromosome 3. Using chromosome banding, fluorescence in situ hybridization, array-based comparative genomic hybridization, global gene expression, and real-time quantitative PCR analyses, we identified the breakpoint regions on chromosomes 1 and 10, demonstrated and delineated the commonly amplified region on chromosome 3, and assessed the consequences of these alterations for gene expression. The breakpoints in the t(1;10) mapped to TGFBR3 in 1p22 and in or near MGEA5 in 10q24, resulting in transcriptional up-regulation of NPM3 and particularly FGF8, two consecutive genes located close to MGEA5. The ring chromosomes contained a commonly amplified 1.44 Mb region in 3p11-12, which was associated with increased expression of VGLL3 and CHMP2B. The identified genetic aberrations were not confined to MIFS; an identical t(1;10) was also found in a case of HFT and the amplicon in 3p was seen in an IMFH.

Purpose: Ezrin is a cytoskeleton linker protein that is actively involved in regulating the growth and metastatic capacity of cancer cells. It has recently been reported to be involved in dissemination of pediatric soft tissue sarcoma (STS). Experimental Design:To further evaluate the prognostic value of ezrin in STS progression, we screened 50 primary STSs of high malignancy grade using immunohistochemistry. At the initial surgery, all patients were without local or distant metastasis. The expression was then compared with the outcome during follow-up for at least 4 years or until the patients' death. Results: Twenty-five of the 50 STSs analyzed (50%) showed ezrin immunoreactivity in the membrane and cytoplasm of the tumor cells. A significant association was shown between positive expressions of ezrin and death in disease as well as overall survival (P = 0.014 and 0.007, respectively). Similarly, ezrin expression was significantly associated with development of distant metastasis during follow-up (P = 0.031), also excluding locally recurrent disease (P = 0.049). The relative abundance of metastasis in ezrin-positive cases was observed both over time and irrespective of time. In comparison with clinical, histopathologic, and genetic characteristics of the STSs, ezrin expression was found to correlate significantly with an infiltrative growth pattern outside the tumor capsule as well as with copy number gain of chromosomal region 9cen-q22. Conclusion: Our findings suggest that ezrin immunoreactivity could be valuable as an additional prognostic marker in highly malignant STSs and support a causative role of ezrin in STS tumor dissemination.

Purpose: Uveal melanoma has a high mortality rate due to a high incidence of metastasis (up to 50%) which preferentially occurs in the liver. Conventional chemotherapy being the only therapeutic option today against metastatic uveal melanoma, has not proved to be effective. Therefore, new molecular targets important for malignant phenotype of uveal melanoma have to be found to design efficient pharmacologic agents. Experimental Design: We previously reported data indicating that the insulinlike growth factor-1 receptor (IGF-IR) is a metastasis predictor as well as a therapeutic target for uveal melanoma. In the present study, we made use of the cyclolignan picropodophyllin (PPP), which is an inhibitor of the IGF-IR. Result: We showed that PPP efficiently block growth and viability of uveal melanoma cells in cultures and causes tumor regression in xenografted mice. In addition, treatment with PPP inhibited several mechanism involved in metastasis, including tumor cells adhesion to extracellular matrix proteins, activity and expression of matrix metalloproteinase 2, and cell migration as well as invasion through basement membranes and endothelial cell layer. Furthermore, PPP significantly delayed established of uveal melanoma tumor and drastically reduced the indence of liver metastasis in mice. Conclusions: Our data suggest that IGR-IR is crucial for growth and survival as well as invasion and metastasis of uveal melanoma cells. Targeting this receptor may therefore comprise a strategy to treat ongoing disease (today incurable) as well as a strategy to prevent development of metastases in patients with primary disease.

SFTs were investigated for STAT6 immunoreactivity using a monoclonal antibody. STAT6 immunocytochemistry was also investigated in schwannomas and spindle cell lipomas. Cytopathologic and clinical characteristics were described. RESULTS:Nineteen benign and 9 malignant SFTs were identified. Both benign and malignant SFTs had a female predominance (female-to-male ratio, 2.8:1 and 1.25, respectively). Localization varied, and approximately one-half of the extrapleural tumors were located in the extremities and frequently were intramuscular. Benign and malignant primary tumors had limited differences in cytologic presentation, the most notable feature being nuclear pleomorphism. Cytomorphologic features included low-to-moderate cellularity of mixed oval, elongated, round, and stellate cells with pink collagenous stroma and hypercellular clusters with infrequent atypia. In metastatic SFTs, the cytopathology was suggestive of sarcoma.Immunohistochemistry revealed nuclear STAT6 immunoreactivity in SFTs (n 5 5) with cytoplasmic reactivity in cytologic mimickers. CONCLUSIONS: Benign and malignant SFTs have common cytopathologic features, and the ability to distinguish between them is limited. Nuclear STAT6 immunoreactivity is a valuable cytologic marker for SFTs. Cancer Cytopathol 2018;126:36-43.