Altered Expression Pattern of Myocyte Enhancer Factor (MEF2) in Benign and Malignant Cartilaginous Tumors
GS Yu, L Balos, M de Peralta-Venturina, TJ Kuntzman, RK Malhotra, EG Bernacki, M Amin. William Beaumont Hospital, Royal Oak, MI; University at Buffalo, Buffalo, MI
Background: MEF2 consists of four isoforms-MEF2A, 2B, 2C and 2D which are important regulators for tissue differentiation and signal responsiveness, in skeletal /cardiac muscle, endothelial cells, brain and cartilage. Suppression of MEF2C resulted in impairment of cartilage development in MEF2C +/- mice and this effect can be augmented by deletion of one MEF2D allele in MEF2C+/- mice. MEF2C over-expression caused precocious chondrocyte hypertrophy and dwarfism. We studied MEF2 expression in benign and malignant cartilaginous lesions with a desire to explore differential expression and thereby evaluate its role in the development of these lesions.
Design: Enchondromas (7), chondromatosis (3), grade I (12), grade II (8) and grade III/dedifferentiated (9) chondrosarcomas were selected for analysis. MEF2 antibody (C21, Santa Cruz, CA) was tested with appropriate controls. Staining results were assessed for intensity (strong, intermediate, weak or negative) and extent. Also noted was staining localization (cytoplasmic and/or nuclear staining).
Results: In benign chondroma and low grade chondrosarcoma , the staining of MEF2 is weaker and nuclear in cellular area but negative in hypocellular hyaline cartilaginous areas. In Grade II chondrosarcoma and chondromatosis the nuclear staining was diffuse and strong. In dedifferentiated chondrosarcoma , MEF2 was expressed not only in the malignant chondrocytes but also in the spindle sarcomatous areas where staining became preferentially cytoplasmic. In all lesions, the staining was prominent in cellular areas but weak or negative in hypocellular hyaline cartilaginous areas.
Conclusions: MEF2 was strongly expressed in cellular proliferating chondrocytes compared to the mature appearing cartilaginous areas. MEF2 expression correlated with cellularity of a lesion whether benign or malignant. In dedifferentiated chondrosarcoma preferential cytoplasmic staining was noted. Our results suggest MEF2 is involved in proliferation of chondrocytes and in the oncogenesis of cartilaginous tumors in humans.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 218, Tuesday Afternoon