Asunto(s)
Huesos/metabolismo , Displasia Fibrosa Monostótica/diagnóstico , Displasia Fibrosa Monostótica/metabolismo , Fluorodesoxiglucosa F18/metabolismo , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/patología , Huesos/patología , Niño , Diagnóstico Diferencial , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/metabolismo , Humanos , MasculinoRESUMEN
To investigate the relationship between osteofibrous dysplasia (OFD) and adamantinoma, we analyzed the expression of several proto-oncogene products and extracellular matrix proteins by immunohistochemistry and correlated our results with histological and ultrastructural findings. C-fos and c-jun, but not c-Met, were observed in OFD and in the fibrous and epithelial components of differentiated and classical adamantinomas. Staining for collagen IV, laminin and galectin-3, a laminin binding protein was seen in OFD and around cell nests in adamantinoma. E-, P-, and N-cadherin expression was found in all cases of classical adamantinoma, but not in differentiated adamantinoma or OFD. Osteonectin was detected in both the epithelial and fibrous components of adamantinomas, but osteopontin and osteocalcin were not seen in classical adamantinomas. The results show common expression of a number of oncoproteins and bone matrix proteins in adamantinoma and OFD, some of which are associated with mesenchymal-to-epithelial cell transformation. These findings would be in keeping with the hypothesis that OFD represents a precursor lesion of adamantinoma. Differential expression of a number of bone matrix protein in adamantinoma may also be of diagnostic use in distinguishing these 2 lesions immunohistochemically.
Asunto(s)
Ameloblastoma/metabolismo , Neoplasias Óseas/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Displasia Fibrosa Monostótica/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas Proto-Oncogénicas c-jun/metabolismo , Adolescente , Adulto , Ameloblastoma/patología , Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/patología , Niño , Preescolar , Femenino , Displasia Fibrosa Monostótica/patología , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Osteonectina/metabolismo , Proto-Oncogenes MasRESUMEN
The NF1 (neurofibromatosis type 1, or von Recklinghausen disease) gene, is a tumor-suppressor gene, and its product, neurofibromin, down-regulates ras protein by its guanosine triphosphatase-activating protein (GAP)-related domain. Osteofibrous dysplasia (OFD) is characterized by fibroblast-like spindle cells and osseous tissue and is generally seen in the tibia or fibula during childhood. The precise nature of OFD remains controversial. Cosegregations of OFD and NF1 have been reported, and it has been surmised that OFD is associated with the NF1 gene. We studied the expressions of NF1 gene product (neurofibromin) and so-called Schwann cell markers (S-100 protein, Leu-7) in 17 cases of OFD immunohistochemically. Ten cases of fibrous dysplasia (FD) were also used for the purpose of comparison. Five OFD and 7 FD cases were analyzed for NF1 gene mutation at codon 1423, which is a GAP-related domain, by single-strand conformation polymorphism. Fibroblast-like cells of OFD showed the expression of neurofibromin (5 of 17), S-100 protein (9 of 17), and Leu-7 (5 of 17), and those of FD did not show these expressions, with the exception of 1 case that showed Leu-7 expression. Regarding the OFD cases, significant correspondence was found between cases showing expression of neurofibromin and S-100 protein, between cases showing expression of neurofibromin and Leu-7, and between cases showing expression of S-100 protein and Leu-7 (P < .01). NF1 gene mutation at codon 1423 was not detected in either the OFD (0 of 5) or FD (0 of 7) cases. These results seem to suggest the possible involvement of neurofibromin in the development of OFD, which is associated with the expression of Schwann cell markers (S-100 protein and Leu-7). Furthermore, NF1 gene mutation at codon 1423 did not seem to be related to OFD.
Asunto(s)
Antígenos CD57/metabolismo , Displasia Fibrosa Monostótica/genética , Displasia Fibrosa Monostótica/metabolismo , Genes de Neurofibromatosis 1 , Neurofibromina 1/metabolismo , Proteínas S100/metabolismo , Adolescente , Adulto , Antígenos CD57/inmunología , Núcleo Celular/metabolismo , Niño , Preescolar , Codón , Análisis Mutacional de ADN , Femenino , Displasia Fibrosa Monostótica/patología , Displasia Fibrosa Poliostótica/genética , Displasia Fibrosa Poliostótica/metabolismo , Displasia Fibrosa Poliostótica/patología , Humanos , Inmunohistoquímica , Lactante , Masculino , Mutación , Neurofibromina 1/inmunología , Proteínas S100/inmunología , Tibia/metabolismo , Tibia/patologíaRESUMEN
Recent advances have been made in the cellular and molecular mechanisms involved in monostotic and polyostotic fibrous dysplasia, a rare nonmalignant disease causing bone deformations and fractures. The molecular basis of fibrous dysplasia has been clarified when mutations affecting the stimulatory alpha subunit of G protein (Gs) have been found in dysplastic bone lesions. The histological analysis of dysplastic lesions revealed that the mutations in Gsalpha caused abnormalities in cells of the osteoblastic lineage and therefore in the bone matrix. Further in vitro analyses of bone cells from mutant dysplastic bone lesions revealed that the abnormal deposition of immature bone matrix in fibrous dysplasia results from decreased differentiation and increased proliferation of osteoblastic cells. Finally, the signaling pathway involved in these osteoblastic abnormalities has been identified. It is now apparent that the constitutive elevation in cAMP level induced by the Gsalpha mutations leads to alterations in the expression of several target genes whose promoters contain cAMP-responsive elements, such as c-fos, c-jun, Il-6 and Il-11. This in turn affects the transcription and expression of downstream genes and results in the alterations of osteoblast recruitment and function in dysplastic bone lesions. These mechanisms provide a cellular and molecular basis for the alterations in bone cells and bone matrix in fibrous dysplasia.
Asunto(s)
Displasia Fibrosa Ósea/etiología , Displasia Fibrosa Ósea/patología , Adenilil Ciclasas/metabolismo , AMP Cíclico/metabolismo , Displasia Fibrosa Ósea/genética , Displasia Fibrosa Ósea/metabolismo , Displasia Fibrosa Monostótica/etiología , Displasia Fibrosa Monostótica/genética , Displasia Fibrosa Monostótica/metabolismo , Displasia Fibrosa Monostótica/patología , Displasia Fibrosa Poliostótica/etiología , Displasia Fibrosa Poliostótica/genética , Displasia Fibrosa Poliostótica/metabolismo , Displasia Fibrosa Poliostótica/patología , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Humanos , Modelos Biológicos , Mutación , Osteoblastos/patologíaRESUMEN
To elucidate the precise origin and characteristics of the epithelial components of osteofibrous dysplasia (OF) and adamantinoma (AD), the expression of transforming growth factor (TGF)-beta1, beta2 and beta3 and cytokeratin (CK) subtypes were studied in five cases of AD and 18 cases of OF by immunohistochemistry. CK1 was expressed in 10 out of 18 OF cases; CK5 was expressed in one OF case; CK14 was positively stained in 10 cases of OF; CK19 was positively stained in 16 OF cases; CK1 was expressed in three out of five AD cases; CK5 was expressed in one case of AD; CK14 was positively stained in four AD cases; and CK19 was positively stained in five AD cases. In OF, TGF-beta1, beta2 and beta3 were expressed in both fibroblasts and osteoblasts. In AD, TGF-beta1, beta2 and beta3 were expressed in both epithelial and fibrous components. These results suggest that epithelial components of AD and OF share epidermal characteristics, CK1, express basal cell phenotype and cytokeratins 5, 14 and 19. In addition to these epithelial characteristics, strong immunoreactivity for TGF-beta poses the possibility of TGF-beta promotion of basal cell phenotype expression for the epithelial components in OF and AD.
Asunto(s)
Neoplasias Óseas/metabolismo , Displasia Fibrosa Monostótica/metabolismo , Queratinas/metabolismo , Neoplasias Glandulares y Epiteliales/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Adolescente , Adulto , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Niño , Preescolar , Femenino , Displasia Fibrosa Monostótica/patología , Displasia Fibrosa Monostótica/cirugía , Peroné/patología , Peroné/cirugía , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/cirugía , Fenotipo , Tibia/patología , Tibia/cirugíaRESUMEN
In this paper, the etiology of monostotic fibrous dysplasia and McCune-Albright syndrome is explained. Both monostotic fibrous dysplasia and McCune-Albright syndrome are sporadically occurring disorders in which a mutation in the GNAS1 gene occurs postzygotically in a somatic cell. All cells descended from the mutated cell can manifest features of McCune-Albright syndrome or fibrous dysplasia. Cells descended from non-mutated cells develop into normal tissues. Thus, the clinical pattern is variable in distribution and appearance. More generalized vs more localized expression depend on (a) how small or how large the cell mass is during embryogenesis when the mutation occurs and (b) where in the cell mass the mutation occurs. Topics discussed include G proteins and their receptors, cycling of stimulatory G protein between active and inactive forms, and specific mutations in GNAS1. We also discuss four possibilities: (a) Are there masked mutations? (b) Are there effects of imprinting? (c) Are there non-classical mutations? and (d) Is fibrous dysplasia a neoplasm?
Asunto(s)
Displasia Fibrosa Monostótica/etiología , Displasia Fibrosa Poliostótica/etiología , Displasia Fibrosa Monostótica/clasificación , Displasia Fibrosa Monostótica/genética , Displasia Fibrosa Monostótica/metabolismo , Displasia Fibrosa Poliostótica/genética , Displasia Fibrosa Poliostótica/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Subunidades alfa de la Proteína de Unión al GTP Gs/metabolismo , Impresión Genómica/genética , Humanos , Mutación/genética , Terminología como AsuntoRESUMEN
Fibrous dysplasia of the facial bones frequently occurs in the maxilla around the time of puberty and becomes inactive when skeletal growth is completed. A case of fibrous dysplasia of the maxilla and sphenoidal-temporal bone in a 19 year-old male was studied, in terms of the presence of estradiol, testosterone and dihydrotestosterone, using the peroxidase-antiperoxidase method. This case underwent partial surgical resection, for cosmetic deformity, of the maxillary tumor which, however, relapsed to preoperative size within three weeks. Estradiol and testosterone were strongly positive and dihydrotestosterone was slightly positive in the tumor cells. Sex hormones were apparently present in the tumor cells and exerted a strong influence on the growth of the fibrous dysplasia.
Asunto(s)
Huesos Faciales , Displasia Fibrosa Monostótica/metabolismo , Hormonas Esteroides Gonadales/metabolismo , Adulto , Dihidrotestosterona/metabolismo , Estradiol/metabolismo , Humanos , Inmunohistoquímica , Masculino , Testosterona/metabolismoRESUMEN
Children with fibrous dysplasia have specific areas of local bony overgrowth. The in vitro metabolism of osteoclasts obtained from involved disease areas of two patients with idiopathic monostotic fibrous dysplasia and one patient with polyostotic fibrous dysplasia were compared with osteoclasts isolated from noninvolved bone in the same individuals and normal controls. The osteoclasts from the involved regions formed similar resorption lacunae compared with osteoclasts isolated from both normal and noninvolved bone. Calcium release into the media, a function of cell-mediated resorption, was decreased in involved osteoclasts compared with osteoclasts derived from normal or noninvolved bone (p < 0.05). Osteoclasts from regions of in vivo abnormal growth exhibited normal mineral metabolism in vitro.