Ossifying fibroma vs fibrous dysplasia of the jaw: molecular and immunological characterization.
Ossifying fibroma and fibrous dysplasia of the jaw are maxillofacial fibro-osseous lesions that should be distinguished each other by a pathologist because they show distinct patterns of disease progression. However, both lesions often show similar histological and radiological features, making distinction between the two a diagnostic dilemma. In this study, we performed immunological and molecular analyses of five ossifying fibromas, four cases of extragnathic fibrous dysplasia, and five cases of gnathic fibrous dysplasia with typical histological and radiographic features. First, we examined the difference between fibrous dysplasia and ossifying fibroma in the expression of Runx2 (which determined osteogenic differentiation from mesenchymal stem cells) and other osteogenic markers. Fibroblastic cells in fibrous dysplasia and ossifying fibroma showed strong Runx2 expression in the nucleus. The bone matrices of both lesions showed similar expression patterns for all markers tested except for osteocalcin. Immunoreactivity for osteocalcin was strong throughout calcified regions in fibrous dysplasia, but weak in ossifying fibroma lesions. Second, we performed PCR analysis with peptide nucleic acid (PNA) for mutations at the Arg(201) codon of the alpha subunit of the stimulatory G protein gene (GNAS), which has reported to be a marker for extragnathic fibrous dysplasia. All nine cases of extragnathic or gnathic fibrous dysplasia were positive for this mutation. On the other hand, none of the five cases of ossifying fibroma showed the mutation. These findings indicate that although fibrous dysplasia and ossifying fibroma are similar disease entities, especially in the demonstration of the osteogenic lineage in stromal fibroblast-like cells, they show distinct differences that can be revealed by immunohistochemical detection of osteocalcin expression. Furthermore, PCR analysis with PNA for GNAS mutations at the Arg(201) codon is a useful method to differentiate between fibrous dysplasia and ossifying fibroma.
Toyosawa
Satoru
S
Department of Oral Pathology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan. toyosawa@dent.osaka-u.ac.jp
Yuki
Michiko
M
Kishino
Mitsunobu
M
Ogawa
Yuzo
Y
Ueda
Takafumi
T
Murakami
Shumei
S
Konishi
Eiichi
E
Iida
Seiji
S
Kogo
Mikihiko
M
Komori
Toshihisa
T
Tomita
Yasuhiko
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002864:Chromogranins; D050657:Core Binding Factor alpha Subunits / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D018214:Fibroma, Ossifying / Q000235:genetics* / Q000473:pathology*; D005357:Fibrous Dysplasia of Bone / Q000235:genetics* / Q000473:pathology*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007573:Jaw Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015675:Osteocalcin / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D002864:Chromogranins; D050657:Core Binding Factor alpha Subunits; D015675:Osteocalcin; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs