Expression of Kruppel-Like Factor 4 in Normal Bone Marrow and Its Utility in the Evaluation of Monocytic Neoplasms
JM Klco, FH Kreisel, A Hassan, T Nguyen, JL Frater. Washington University School of Medicine, St Louis, MO
Background: Kruppel-like factor 4 (KLF4), a member of the Kruppel-like family of transcription factors, has a known role in epithelial differentiation but also is important in the differentiation of monocytes. The expression pattern of KLF4 in normal bone marrow, as well as in neoplasms with monocytic differentiation, is unknown.
Design: KLF-4 expression was assessed by IHC in 93 paraffin-embedded bone marrow core biopsies, including 17 cases of acute monocytic leukemia (FAB M5), 7 acute myeloid leukemias (AMLs) with 11q23 (MLL) abnormalities, 23 acute myelomonocytic leukemias (FAB M4), 4 AMLs with inv(16), 15 non-monocytic AMLs, 21 chronic myelomonocytic leukemias (CMMLs) and 6 normal bone marrow controls. Expression was scored as positive if present in the nuclei of more than 10% of the bone marrow mononuclear cells. The expression pattern of KLF4 was compared to CD68 (KP-1) and CD163.
Results: KLF4 expression in normal bone marrow was limited to scattered interstitial monocytes/ macrophages (less than 10% of overall cellularity), and a subset of endothelial cells. No consistent KLF4 expression was present in maturing granulocytes or the erythroid or megakaryocytic series, similar to CD163. CD68 immunostains highlighted >10% of the cells in all the control marrow specimens. KLF4 was expressed in 44/73 (60%) of the neoplasms with monocytic features and in 10/15 (66%) of non-monocytic leukemias, while CD68 was positive in 65/73 (89%) of monocytic tumors. High CD68 (>10%) expression was detected in all the non-monocytic neoplasms, predominantly on non-neoplastic macrophages. CD163 was positive in 21/73 (29%) of the monocytic neoplasms. No significant difference in KLF4 expression was noted in the immature (i.e. FAB M5) versus the mature (i.e. CMML) monocytic neoplasms or among the AML subtypes with monocytic features. In addition, the staining intensity of KLF4 was frequently higher in non-neoplastic monocytes in normal bone marrow compared to neoplastic monocytes.
Conclusions: In normal bone marrow KLF4 expression is specific for the monocyte lineage with clear nuclear expression by IHC. While not as sensitive for monocytic leukemias as CD68 (94% vs 60%, p<0.05), KLF4 immunostains have less obscuring background staining. KLF4 is more sensitive for monocytic neoplasms than CD163 (60% vs 31%, p<0.05) but not as specific (33% vs 80%, p<0.05). KLF4 represents a novel monocyte marker useful in the workup of potential monocytic neoplasms.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 185, Monday Morning