Ki-67 Expression in megakaryocytes: A new prognostic marker in Myelodysplastic Syndromes

An elevated Ki-67 proliferation index is a known marker of adverse prognosis in several solid and hematological tumors, but its role in Myelodysplastic Syndromes (MDS) remains underexplored. This study aimed to quantify Ki-67 expression across hematopoietic lineages in bone marrow biopsies (BMB) from MDS patients and assess its correlation with clinical features and outcomes. We performed single and double immunohistochemistry for Ki-67 with CD34, CD71, MPO, and Factor VIII on BMB samples from 73 patients diagnosed with MDS or oligoblastic acute myeloid leukemia (AML) at a single center. The cohort had a median 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 International Prognostic Scoring System scores ≥ 3.5. Median overall survival (OS) and progression-free survival (PFS) were 2.8 and 2.7 years, respectively. Ki-67 expression upper 10% 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, coexpression Ki-67 with 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 model. Ki-67 expression in megakaryocytes is a potential independent prognostic marker that requires validation in larger prospective cohorts and may reflect a bone marrow microenvironment dysregulation.