TWIST1 Protein Expression in Plasma Cell Neoplasias and Plasmablastic Lymphoma

BACKGROUND. In malignant neoplasms, overexpression of transcription regulator TWIST1 is associated with high metastasis rate and spread of tumor cells as well as their evasion of apoptosis and chemoresistance occurrence. At present, there are essentially no data on TWIST1 protein expression in plasma cell neoplasias (PN) and plasmablastic lymphoma (PBL). AIM. To determine the rate and pattern of TWIST1 expression based on the analysis of bone marrow core biopsy samples and biopsy samples of tumor substrate from patients with various PNs and PBLs as well as to compare TWIST1 expression with t(4;14)(p16;q32) and the mutation status of KRAS, NRAS, and BRAF genes. MATERIALS & METHODS. The study enrolled 235 patients with various PNs aged 19–87 years (median 56 years) examined at the National Research Center for Hematology in the period of 2018–2025. Male/female ratio was 1.53:2 (102 men and 133 women). Distribution of patients according to the nosologies was as follows: monoclonal gammopathy of undetermined significance (MGUS; n = 28), smoldering myeloma (n = 31), multiple myeloma (n = 102), plasmacytoma (PM; n = 20), plasma cell leukemia (PCL; n = 19), and PBL (n = 35). Paraffin block sections of bone marrow core/tumor biopsy samples were histologically and immunohistochemically analyzed using anti-TWIST1 antibodies. KRAS and NRAS mutations in bone marrow CD138+ cells were detected by Sanger sequencing. The mutation profile of gene BRAFV600E was analyzed by allele-specific real-time PCR. RESULTS. The proportion of TWIST1-positive plasma cells as well as the intensity and pattern of its expression considerably varied in PNs. The highest proportion of positive plasma cells was observed in PCL (0–30 %, median 4.4 %), PM (0–30 %, median 4.4 %), and PBL (0–15 %, median 4.9 %). Intense reaction also predominated in tissues from PM (12/20; 60 %) and PBL (25/35; 71.4 %) patients. Monomorphic reaction was typically detected in PCL (10/19; 52.6 %) and PBL (26/35; 74.3 %). The study demonstrated the potential of TWIST1 expression to be used as an additional criterion for MGUS diagnosis and for differential diagnosis of PBL and PN. No significant association of ТWIST1 expression with either t(4;14)(p16;q32) or mutation status of KRAS, NRAS, and BRAF was noted. CONCLUSION. Immunohistochemical analysis of bone marrow core/tumor substrate biopsy samples with anti-TWIST1 antibodies can be used as an additional criterion for differential diagnosis of various PNs.