bims-myxlip 2021-12-05 papers

Issue of 2021–12–05
two papers selected by
Laura Mannarino, Humanitas Research

J Histotechnol. 2021 Nov 30. 1-10

Expression of CTAG1B clone EPR13780 versus DDIT3 gene rearrangement distinguishes myxoid liposarcoma from its mimics with detection of novel DDIT3 gene copy number variations.

Marwa M Abdelaziz, Hanan Y Tayel, Amany Abdel-Bary, Omnia M Badawy.

Myxoid liposarcoma (MLPS) has different patterns that are often difficult to distinguish from other soft tissue lesions. MLPS is characterized by a reciprocal translocation involving the DNA Damage Inducible Transcript 3 gene (DDIT3) that can be detected using fluorescent in situ hybridization (FISH). Recently, the marker for cancer testis antigen 1b (CTAG1B) was found to be expressed in MLPS. The aim of the present study was to assess the potential use immunohistochemistry (IHC) for CTAG1B expression and DDIT3 rearrangement to diagnose MLPS and distinguish it from similar lesions. Out of 29 cases including MLPS and its mimics, CTAG1B was expressed in 92.86% of cases of MLPS and 20% of its mimics. DDIT3 rearrangement was 100% sensitive and 92.86% specific in distinguishing MLPS from its mimics. The DDIT3 rearrangement was found to be more sensitive but less specific than cytoplasmic expression of CTAG1B marker. DDIT3 polysomy and amplification were detected in some cases. Therefore, both CTAG1B expression and FISH for DDIT3 gene can be used to distinguish MLPS from similar tumors. The use of both immunohistochemistry for CTAG1B in addition to DDIT3 gene rearrangement detection by FISH was more specific than using either of them alone. However, the DDIT3 gene rearrangement alone was the most sensitive test for distinguishing MLPS from its mimics.

Keywords: CTAG1B; DDIT3; FISH; Myxoid liposarcoma; copy number variations; gene rearrangement; immunohistochemistry; soft tissue tumors

DOI: https://doi.org/10.1080/01478885.2021.2004294

J Hematol Oncol. 2021 Dec 02. 14(1): 202

GSK3-beta as a candidate therapeutic target in soft tissue sarcomas.

S Verbeke, R Perret, V Chaire, E Richard, V Velasco, F Giles, L Cavalcante, A Italiano.

Soft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3β gene and protein expression in two independent cohorts of patients with STS. We then treated STS cell lines and mice xenografts with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. We demonstrated that 9-ING-41 treatment induced significant STS cells apoptosis and was synergistic in vivo when combined with chemotherapy. Mechanistically, 9-ING-41 induces significant apoptosis of STS cells via suppression of NF-κB-mediated X-linked inhibitor of apoptosis protein (XIAP) expression. These data support the inclusion of patients with STS in clinical studies of 9-ING-41 alone and in combination with chemotherapy.

Keywords: 9-ING-41; Glycogen synthase kinase 3β; Soft tissue sarcomas

DOI: https://doi.org/10.1186/s13045-021-01215-x