KI-67 EXPRESSION IN MEGAKARYOCYTES IS ASSOCIATED WITH HIGHER RISK OF PROGRESSION AND SHORTER OVERALL SURVIVAL IN MYELODYSPLASTIC SYNDROMES

While higher Ki-67 proliferation index is associated with poor prognosis in solid tumors, few studies have evaluated the role of this parameter in MDS. Furthermore, the role of specific hematopoietic lineage undergoing proliferation in MDS has not been well studied. The aim of this study is to quantify Ki-67 expression in different hematopoietic lineages in bone marrow biopsies from MDS patients and investigate its association with clinical variables and outcomes. Isolated and double immunohistochemistry for Ki-67, along with CD34, CD71, MPO, Factor VIII, were performed on BMB samples from MDS patients and oligoblastic AML diagnosed and followed at a single-center. Correlation between Ki-67 expression and clinical/laboratory parameters, IPSS-R risk score, and outcomes (overall survival [OS] and progression-free survival [PFS]), was analyzed. The cohort had a mean age of 70 years, 56% were male, 81% had de novo MDS, and 15% therapy-related MDS. Abnormal karyotypes were present in 32%, and 52% had IPSS-R scores ≥3.5. Median overall survival (OS) and progression-free survival (PFS) were 2.8 and 2.7 years, respectively. High Ki-67 expression (>10% of hematopoietic cells) occurred in 27% of patients. Coexpression of Ki-67 with CD34, MPO, CD71, and Factor VIII was observed in 79%, 63%, 85%, and 16% of cases, respectively. Notably, Ki-67 expression in Factor VIII+ correlated with higher blast counts, shorter PFS (HR 3.29), and reduced OS (HR 2.96). Incorporating Ki-67/Factor VIII double labeling improved prognostic accuracy when added to the IPSS-R mode. Our findings suggest that Ki-67 expression in megakaryocytes is an independent prognostic marker in MDS and may reflect bone marrow microenvironmental dysregulation.