Molecular pathological study of fibro-osseous lesions of the jaws

Objective: Fibro-osseous lesions of the jaws are the pathologic conditions characterized by the replacement of normal bone by a fibrous connective tissue and mineralized material, which include cemento-ossifying fibroma (COF), fibrous dysplasia (FD) and cemento-osseous dysplasia (COD). The pathogenesis of the lesions has never been defined in more stringent although they are interpreted as diseases representing an overgrowth of primitive mesenchymal cells. Moreover, the lesions usually present a diagnostic dilemma for both clinicians and pathologists because of uncertainties concerning the diagnostic significance of clinical, radiological, and histological features. Recently it was demonstrated that Runx2 determined the lineage of osteoblasts from mesenchymal cells. Hence, Runx2 expression is considered to be a marker of osteoblastic lineage. In turn, Gsa mutation at the Arg²⁰¹codon is thought to underlie the development of FD. In this study, we investigated the Runx2 expression and the occurrence of Gsa mutation in the lesions with a view of the pathological diagnoses. Methods: The formalin-fixed, paraffin-embedded tissue blocks of five COF, seven FD and three COD cases, were used for this study. Tissue sections were used for immunohistochemical studies to identify the Runx2-expressing cells using monoclonal antibody against recombinant Runx2. DNA was extracted from a paraffin-embedded tissue sections. We used the PCR-RFLP procedure to detect Gsa mutation as previously reported. Results: Runx2-positive cells were frequently identified even in the fibrous connective tissue of all cases of COF, FD and COD. The Gsa mutation at the Arg²⁰¹ codon was occurred in all seven cases of FD while no mutation at the Arg²⁰¹ codon was seen in all cases of COF and COD. Conclusions: Our findings suggest that fibro-osseous lesions are interpreted as a disease of cells in the osteoblastic lineage. Moreover, the detection of the Gsa mutation is useful to differentiate FD from COF and COD.