RESUMEN
BACKGROUND: Fibrous dysplasia (FD) and cemento-ossifying fibroma (COF) are the most common gnathic fibro-osseous lesions. These diseases exhibit remarkable overlap of several clinicopathological aspects, and differential diagnosis depends on the combination of histopathological, radiographic, and clinical aspects. Their molecular landscape remains poorly characterized, and herein, we assessed their proteomic and phosphoproteomic profiles. METHODS: The quantitative differences in protein profile of FD and COF were assessed by proteomic and phosphoproteomic analyses of formalin-fixed paraffin-embedded tissue samples. Pathway enrichment analyses with differentially regulated proteins were performed. RESULTS: FD and COF exhibited differential regulation of pathways related to extracellular matrix organization, cell adhesion, and platelet and erythrocytes activities. Additionally, these lesions demonstrated distinct abundance of proteins involved in osteoblastic differentiation and tumorigenesis and differential abundance of phosphorylation of Ser61 of Yes-associated protein 1 (YAP1). CONCLUSIONS: In summary, despite the morphological similarity between these diseases, our results demonstrated that COF and DF present numerous quantitative differences in their proteomic profiles. These findings suggest that these fibro-osseous lesions trigger distinct molecular mechanisms during their pathogenesis. Moreover, some proteins identified in our analysis could serve as potential biomarkers for differential diagnosis of these diseases after further validation.
Asunto(s)
Cementoma , Fibroma Osificante , Displasia Fibrosa Ósea , Cementoma/diagnóstico , Cementoma/patología , Diagnóstico Diferencial , Fibroma Osificante/metabolismo , Displasia Fibrosa Ósea/patología , Humanos , ProteómicaRESUMEN
Ossifying fibromyxoid tumors (OFMTs) are rare tumors of uncertain origin and intermediate (rarely metastasizing) biologic potential, with characteristic morphology of an encapsulated tumor containing polygonal cells in an abundant fibromyxoid matrix surrounded by a peripheral layer of metaplastic lamellar bone. FNA cytology of OFMT has not been sufficiently reported and till date cytological features of only seven cases have been reported so far. We report another case of OFMT in a 55-year-old female presenting with longstanding swelling in thigh. On fine-needle aspiration, a tumor with moderate cellularity and myxoid areas was seen; coupled with compatible radiological findings, a diagnosis of OFMT was suggested. Establishing a correct diagnosis is important as although OFMT is benign in nature, local recurrences or rarely distant metastasis have been seen of this tumor. Hence, a high degree of suspicion with radiological correlation is of utmost importance for identification of this entity.
Asunto(s)
Neoplasias Óseas , Fibroma Osificante , Neoplasias de los Tejidos Blandos , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Femenino , Fibroma Osificante/diagnóstico , Fibroma Osificante/metabolismo , Fibroma Osificante/patología , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/metabolismo , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/secundarioRESUMEN
Differential diagnosis among fibrous dysplasias, cemento-ossifying fibromas and cemento-osseous dysplasias is difficult, since there is considerable overlap of histologic features, but also extremely important, since they differ greatly in etiology, clinical behaviour, prognosis and terapeuthic approach. There is no data about the use of immunohistochemistry, a viable and accessible technique, for this purpose. The objective of this study was to investigate, comparatively, the immunohistochemical expression of major non-collagenous proteins (osteonectin [ON], osteopontin [OP], bone sialoprotein [BSP] and osteocalcin [OC]) of mineralized tissue extracellular matrix in 22 cases of fibrous dysplasias, 16 of cemento-ossifying fibromas and 16 of cemento-osseous dysplasias. ON maintained the same expression profile in all cases; the staining for OP was negative in fusiform cells producing cementoid globules and weak, as well as heterogeneous, in high mineralized matrixes; there was negativity for BSP in cementoid globules and in the fusiform cells that produce them, differently from the strong positive expression found in the majority of bone trabeculae and their peripheral cuboidal osteoblasts; and finally, the immuno-reactivity for OC was weak, except in cuboidal osteoblasts and osteocytes. We can conclude that the nature of mineralized structure and the cellular phenotype are much more responsible for variability in immunohistochemical profile than the type of lesion (fibrous dysplasias, cemento-ossifying fibromas and cemento-osseous dysplasias) which makes difficult, at least for a while, the use of these proteins with diagnosis purpose.
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Cementoma/diagnóstico , Fibroma Osificante/diagnóstico , Displasia Fibrosa Ósea/diagnóstico , Sialoproteína de Unión a Integrina/metabolismo , Osteocalcina/metabolismo , Osteonectina/metabolismo , Osteopontina/metabolismo , Huesos/patología , Cementoma/metabolismo , Cementoma/patología , Diagnóstico Diferencial , Fibroma Osificante/metabolismo , Fibroma Osificante/patología , Displasia Fibrosa Ósea/metabolismo , Displasia Fibrosa Ósea/patología , HumanosRESUMEN
BACKGROUND: Cemento-ossifying fibroma (COF) is a benign fibro-osseous neoplasm of uncertain pathogenesis, and its treatment results in morbidity. MicroRNAs (miRNA) are small non-coding RNAs that regulate gene expression and may represent therapeutic targets. The purpose of the study was to generate a comprehensive miRNA profile of COF compared to normal bone. Additionally, the most relevant pathways and target genes of differentially expressed miRNA were investigated by in silico analysis. METHODS: Nine COF and ten normal bone samples were included in the study. miRNA profiling was carried out by using TaqMan® OpenArray® Human microRNA panel containing 754 validated human miRNAs. We identified the most relevant miRNAs target genes through the leader gene approach, using STRING and Cytoscape software. Pathways enrichment analysis was performed using DIANA-miRPath. RESULTS: Eleven miRNAs were downregulated (hsa-miR-95-3p, hsa-miR-141-3p, hsa-miR-205-5p, hsa-miR-223-3p, hsa-miR-31-5p, hsa-miR-944, hsa-miR-200b-3p, hsa-miR-135b-5p, hsa-miR-31-3p, hsa-miR-223-5p and hsa-miR-200c-3p), and five were upregulated (hsa-miR-181a-5p, hsa-miR-181c-5p, hsa-miR-149-5p, hsa-miR-138-5p and hsa-miR-199a-3p) in COF compared to normal bone. Eighteen common target genes were predicted, and the leader genes approach identified the following genes involved in human COF: EZH2, XIAP, MET and TGFBR1. According to the biology of bone and COF, the most relevant KEGG pathways revealed by enrichment analysis were proteoglycans in cancer, miRNAs in cancer, pathways in cancer, p53-, PI3K-Akt-, FoxO- and TGF-beta signalling pathways, which were previously found to be differentially regulated in bone neoplasms, odontogenic tumours and osteogenesis. CONCLUSION: miRNA dysregulation occurs in COF, and EZH2, XIAP, MET and TGFBR1 are potential targets for functional analysis validation.
Asunto(s)
Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Fibroma Osificante/genética , Fibroma Osificante/metabolismo , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , MicroARNs/genética , Adolescente , Adulto , Biología Computacional , Regulación hacia Abajo , Proteína Potenciadora del Homólogo Zeste 2/genética , Femenino , Factores de Transcripción Forkhead/metabolismo , Estudios de Asociación Genética , Humanos , Masculino , MicroARNs/clasificación , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Tumores Odontogénicos , Osteogénesis , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas c-met/genética , ARN no Traducido , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/genética , Proteína p53 Supresora de Tumor/metabolismo , Regulación hacia Arriba , Proteína Inhibidora de la Apoptosis Ligada a X/genética , Adulto JovenRESUMEN
INTRODUCTION: Ossifying fibromyxoid tumor (OFMT) is rare and may present diagnostic difficulty. We describe 26 subcutaneous examples of OFMT emphasizing differential diagnosis and prognostic features. METHODS: Histopathology and follow-up data from archival/consultation cases were reviewed. Prognostic features were assessed according to proposed criteria. RESULTS: Patients (16 female, 10 male) ranged from 26 to 88 years (median 54). The tumors (median 2.3 cm, range 0.8-8.5) involved lower limb (11), trunk (7), head/neck (4), or arm (4). All showed combinations of corded, nested and trabecular patterns in a fibromyxoid stroma. Out of 26 cases 13 had peripheral ossification. Sixteen of 22 cases showed S100 protein expression. Nuclear grade was low (14); intermediate (8) and high (4) while cellularity was low (14); moderate (7) and high (5), with overall good interobserver agreement. Median mitotic rate was 3/50HPF (0-61). Five met criteria for malignant OFMT showing high nuclear grade or high cellularity and mitotic rate >2/50HPF or both. Thirteen OFMTs were atypical. Follow-up (16/26, median 45.5 months, range 8-108) showed that patients with typical OFMT (3) and atypical OFMT (9) remained disease-free. Three malignant examples of OFMT recurred and one metastasized to the lung. No deaths were recorded. CONCLUSIONS: Our results validate proposed prognostic classification of OFMT. Dermatopathologists should be aware of this unusual superficial tumor given its potentially aggressive behavior.
Asunto(s)
Neoplasias Óseas/patología , Fibroma Osificante/patología , Neoplasias de los Tejidos Blandos/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/metabolismo , Proteínas de Unión al ADN/metabolismo , Diagnóstico Diferencial , Femenino , Fibroma Osificante/diagnóstico , Fibroma Osificante/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Variaciones Dependientes del Observador , Proteínas del Grupo Polycomb/metabolismo , Pronóstico , Enfermedades Raras , Proteínas S100/metabolismo , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/metabolismo , Tejido Subcutáneo/metabolismo , Tejido Subcutáneo/patologíaRESUMEN
Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm with uncertain histogenesis. Most cases behave in a clinically benign fashion; however, a small percentage of tumors may locally recur or metastasize. Herein we present a case of a 56-year-old man who presented with an enlarging left groin mass, left inner thigh numbness, burning paresthesia and discomfort in his left groin. The mass sampled by fine- needle aspiration and needle core biopsy. Cytology showed bland-appearing epithelioid cells with round nuclei and fine chromatin, with fragments of fibromyxoid stroma in the background. Immunohistochemical stains performed on the core biopsy showed that the lesional cells were focally positive for S100 protein and negative for desmin, smooth muscle actin, CD34 and cytokeratin AE1/AE3. A benign neoplasm was favored with ossifying fibromyxoid tumor as the main entity in the differential diagnosis. A subsequent resection showed a well-circumscribed 5 cm mass with firm consistency and focal areas of calcifications. Histologically, the tumor had a nodular growth pattern with relatively bland spindle cells containing round to oval nuclei suspended in a variably collagenous to myxoid stroma. Significant ossification and bone formation was also noted. There was no significant atypia, necrosis or increased mitoses. Ossifying fibromyxoid tumors have distinct cytologic features and should be considered in the differential diagnosis of soft tissue tumors with prominent ossification.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Fibroma Osificante/diagnóstico , Fibroma/diagnóstico , Proteínas S100/metabolismo , Neoplasias de los Tejidos Blandos/diagnóstico , Biopsia con Aguja Gruesa , Calcinosis/patología , Células Epitelioides/metabolismo , Células Epitelioides/patología , Fibroma/metabolismo , Fibroma/patología , Fibroma/cirugía , Fibroma Osificante/metabolismo , Fibroma Osificante/patología , Fibroma Osificante/cirugía , Ingle/patología , Ingle/cirugía , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Parestesia/patología , Neoplasias de los Tejidos Blandos/metabolismo , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/cirugíaRESUMEN
Reactive proliferations of the gingiva comprise lesions such as pyogenic granuloma (PG), inflammatory fibroepithelial hyperplasia (IFH), peripheral ossifying fibroma (POF), and peripheral giant cell lesion. Osteopontin (OPN) has a dual role, it promotes mineralization when it is bound to solid substrate, and on the other hand, it inhibits mineralization when it is seen in association with solution. Objectives The study aimed to evaluate the expression of osteopontin in normal gingival tissue and different types of focal reactive proliferations of gingival tissue, and its role in the development of calcification within it. Material and Methods The presence and distribution of osteopontin was assessed using immunohistochemistry in five cases of normal gingival tissue and 30 cases of focal reactive proliferations of gingiva. Results There was no expression of osteopontin in normal subjects. Few cases of pyogenic granuloma, inflammatory fibroepithelial hyperplasia, and all the cases of peripheral ossifying fibroma showed positivity for osteopontin in the inflammatory cells, stromal cells, extracellular matrix, and in the calcifications. Conclusion The expression of osteopontin in all the cases of peripheral ossifying fibroma speculates that the majority of the cases of peripheral ossifying fibroma originate from the periodontal ligament cells. The treatment modalities for peripheral ossifying fibroma should differ from other focal reactive proliferations of gingiva.
Asunto(s)
Encía/metabolismo , Enfermedades de las Encías/metabolismo , Osteopontina/metabolismo , Neoplasias Óseas/metabolismo , Estudios de Casos y Controles , Fibroma Osificante/metabolismo , Tumores de Células Gigantes/metabolismo , Granuloma Piogénico/metabolismo , Humanos , Hiperplasia/metabolismo , Inmunohistoquímica , Valores de ReferenciaRESUMEN
Reactive proliferations of the gingiva comprise lesions such as pyogenic granuloma (PG), inflammatory fibroepithelial hyperplasia (IFH), peripheral ossifying fibroma (POF), and peripheral giant cell lesion. Osteopontin (OPN) has a dual role, it promotes mineralization when it is bound to solid substrate, and on the other hand, it inhibits mineralization when it is seen in association with solution. Objectives The study aimed to evaluate the expression of osteopontin in normal gingival tissue and different types of focal reactive proliferations of gingival tissue, and its role in the development of calcification within it. Material and Methods The presence and distribution of osteopontin was assessed using immunohistochemistry in five cases of normal gingival tissue and 30 cases of focal reactive proliferations of gingiva. Results There was no expression of osteopontin in normal subjects. Few cases of pyogenic granuloma, inflammatory fibroepithelial hyperplasia, and all the cases of peripheral ossifying fibroma showed positivity for osteopontin in the inflammatory cells, stromal cells, extracellular matrix, and in the calcifications. Conclusion The expression of osteopontin in all the cases of peripheral ossifying fibroma speculates that the majority of the cases of peripheral ossifying fibroma originate from the periodontal ligament cells. The treatment modalities for peripheral ossifying fibroma should differ from other focal reactive proliferations of gingiva. .
Asunto(s)
Humanos , Encía/metabolismo , Enfermedades de las Encías/metabolismo , Osteopontina/metabolismo , Neoplasias Óseas/metabolismo , Estudios de Casos y Controles , Fibroma Osificante/metabolismo , Tumores de Células Gigantes/metabolismo , Granuloma Piogénico/metabolismo , Hiperplasia/metabolismo , Inmunohistoquímica , Valores de ReferenciaRESUMEN
BACKGROUND: The peripheral ossifying fibroma (POF) represents one of the most common lesions of the periodontal tissues that may originate from the gingival soft tissues, the periosteum, or the periodontal ligament. AIM: To investigate the immunohistochemical expression of runt-related transcription factor 2 (Runx-2), bone morphogenetic protein-2 (BMP-2), and cementum attachment protein (CAP) in oxytalan-positive POF, to establish the use of POF as an in vivo model for the study of the periodontal ligament. MATERIALS AND METHODS: Thirty tumors that presented clinical and histologic features of POF, as well as oxytalan fibers, were included in the study. Immunohistochemical expression of Runx-2, BMP-2, and CAP was evaluated by light microscopy. RESULTS: Runx-2, BMP-2, and CAP were abundantly expressed by POFs; 22 of 30 tumors expressed positive staining for Runx-2, twenty-six tumors for BMP-2, and twenty-five tumors for CAP. The expression of Runx-2 was abundant in POFs where bone was histologically present (P = 0.04) and of BMP-2 in POFs where dystrophic calcifications were present (P = 0.03). CONCLUSION: It is suggested that oxytalan-positive POFs, purportedly originating from the periodontal ligament, express molecules that are specific to bone and cementum (Runx-2, BMP-2), or cementum only (CAP). Thus, the cell populations present in the lesion belong to the mineralized-tissue-forming cell lineages, the cementoblastic or osteoblastic lineage.
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Proteína Morfogenética Ósea 2/biosíntesis , Neoplasias Óseas/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/biosíntesis , Proteínas de la Matriz Extracelular/biosíntesis , Fibroma Osificante/metabolismo , Neoplasias Gingivales/metabolismo , Proteínas Tirosina Fosfatasas/biosíntesis , Proteína Morfogenética Ósea 2/genética , Neoplasias Óseas/patología , Calcificación Fisiológica , Diferenciación Celular/fisiología , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Cemento Dental/metabolismo , Femenino , Fibroma Osificante/patología , Encía/metabolismo , Encía/patología , Humanos , Inmunohistoquímica , Masculino , Osteoblastos/metabolismo , Ligamento Periodontal/metabolismo , Ligamento Periodontal/patología , Proteínas Tirosina Fosfatasas/genética , Estudios RetrospectivosRESUMEN
INTRODUCTION: The aim of this study was to perform a retrospective study of histopathologic features of a series of cases of pyogenic granuloma (PG), peripheral giant cell lesion (PGCL), and peripheral ossifying fibromas (POF) that constitutes the group called reactional lesions, located in gingiva and alveolar ridge. STUDY DESIGN: Cases of PG, PGCL, and POF were selected for this study. The morphological analysis of the lesions constituted the following: intensity of inflammatory infiltrate (IF), presence of vascular proliferation (VP), fibroblastic proliferation (FP), areas of ulceration (AU), bacterial colony (BC), presence of mineralization (PM), multinucleated giant cells (MGC), hemosiderin deposition (HD), hemorrhage area (HA). RESULTS: Of the 288 cases analyzed, 162 (56.3%) were PG, 72 (25%) were PGCL, and 54 (18.8%) were POF. The IF, VP, AU, and BC were more prominent in PG (85.8%, 98.8%, 91.4%, and 46.9%, respectively) and PM in POFs (98.1%). FP was more frequent in POF (98.1%) and PGCL (100%) and MGC in PGCL (100%), although some cases of POF (7.4%) and PG (0.6%) exhibited MGC. HD was more frequent in PGCL (40.3%) and HA in PG (53.1%). CONCLUSIONS: This study demonstrated that IF, VP, AU, BC, and HA are the common features in PG, MGC, FP, and HD are the most common in PGCL, and PM associated with FP are the most common in POF, which can help in the histopathologic differential diagnosis between these lesions. In addition, it may suggest a possible development and maturation of the PG in POF with reduction in the inflammatory component and increase in the fibrous component.
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Proceso Alveolar , Fibroma Osificante , Encía , Granuloma Piogénico , Neoplasias Maxilomandibulares , Proceso Alveolar/metabolismo , Proceso Alveolar/patología , Proliferación Celular , Femenino , Fibroblastos/metabolismo , Fibroblastos/patología , Fibroma Osificante/metabolismo , Fibroma Osificante/patología , Células Gigantes/metabolismo , Células Gigantes/patología , Encía/metabolismo , Encía/patología , Granuloma Piogénico/metabolismo , Granuloma Piogénico/patología , Humanos , Inflamación/metabolismo , Inflamación/patología , Neoplasias Maxilomandibulares/metabolismo , Neoplasias Maxilomandibulares/patología , Masculino , Estudios RetrospectivosRESUMEN
Hyperparathyroidism Jaw-Tumour Syndrome (HPT-JT) is characterized by primary hyperparathyroidism (PHPT), maxillary/mandible ossifying fibromas and by parathyroid carcinoma in 15% of cases. Inactivating mutations of the tumour suppressor CDC73/HRPT2 gene have been found in HPT-JT patients and also as genetic determinants of sporadic parathyroid carcinoma/atypical adenomas and, rarely, typical adenomas, in familial PHPT. Here we report the genetic and molecular analysis of the CDC73/HRPT2 gene in three patients affected by PHPT due to atypical and typical parathyroid adenomas, in one case belonging to familial PHPT. Flag-tagged WT and mutant CDC73/HRPT2 proteins were transiently transfected in HEK293 cells and functional assays were performed in order to investigate the effect of the variants on the whole protein expression, nuclear localization and cell overgrowth induction. We identified four CDC73/HRPT2 gene mutations, three germline (c.679_680delAG, p.Val85_Val86del and p.Glu81_Pro84del), one somatic (p.Arg77Pro). In three cases the mutation was located within the Nucleolar Localisation Signals (NoLS). The three NoLS variants led to instability either of the corresponding mutated protein or mRNA or both. When transfected in HEK293 cells, NoLS mutated proteins mislocalized with a predeliction for cytoplasmic or nucleo-cytoplasmic localization and, finally, they resulted in overgrowth, consistent with a dominant negative interfering effect in the presence of the endogenous protein.
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Mutación de Línea Germinal , Hiperparatiroidismo Primario/genética , Proteínas de Neoplasias/genética , Señales de Localización Nuclear/genética , Proteínas Supresoras de Tumor/genética , Adolescente , Niño , Citoplasma/genética , Citoplasma/metabolismo , Femenino , Fibroma Osificante/genética , Fibroma Osificante/metabolismo , Fibroma Osificante/patología , Células HEK293 , Humanos , Hiperparatiroidismo Primario/metabolismo , Hiperparatiroidismo Primario/patología , Neoplasias Maxilomandibulares/genética , Neoplasias Maxilomandibulares/metabolismo , Neoplasias Maxilomandibulares/patología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Señales de Localización Nuclear/metabolismo , Transporte de Proteínas/genética , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Abnormal stem cell function makes a known contribution to many malignant tumors, but the role of stem cells in benign tumors is not well understood. Here, we show that ossifying fibroma (OF) contains a stem cell population that resembles mesenchymal stem cells (OFMSCs) and is capable of generating OF-like tumor xenografts. Mechanistically, OFMSCs show enhanced TGF-ß signaling that induces aberrant proliferation and deficient osteogenesis via Notch and BMP signaling pathways, respectively. The elevated TGF-ß activity is tightly regulated by JHDM1D-mediated epigenetic regulation of thrombospondin-1 (TSP1), forming a JHDM1D/TSP1/TGF-ß/SMAD3 autocrine loop. Inhibition of TGF-ß signaling in OFMSCs can rescue their abnormal osteogenic differentiation and elevated proliferation rate. Furthermore, chronic activation of TGF-ß can convert normal MSCs into OF-like MSCs via establishment of this JHDM1D/TSP1/TGF-ß/SMAD3 autocrine loop. These results reveal that epigenetic regulation of TGF-ß signaling in MSCs governs the benign tumor phenotype in OF and highlight TGF-ß signaling as a candidate therapeutic target.
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Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Epigénesis Genética/genética , Fibroma Osificante/metabolismo , Fibroma Osificante/patología , Células Madre Neoplásicas , Proteína smad3/genética , Factor de Crecimiento Transformador beta/genética , Animales , Humanos , Ratones , Células Madre Neoplásicas/citología , Células Madre Neoplásicas/metabolismoRESUMEN
The peripheral ossifying fibroma (POF) is a reactive gingival overgrowth occurring frequently in the anterior maxilla. It originates in the cells of the periodontal ligament and is more common in children and young adults. In the current article a case of gingival over growth, which was thought to be puberty-induced gingivitis was seen in the lower anterior maxillary gingiva. Histology of the excised tissue showed cellular, fibrous connective tissue stroma with calcified osseous calcifications indicative of POF. The definitive diagnosis is established only by histological examination, which revealed the presence of highly cellular connective tissue with focal calcifications. Surgery is the treatment of choice, though the recurrence rate can reach 20% in case of POF. After histological confirmation the recall and clinical evaluation protocol of POF varies due to its increased recurrence rate, which the general dentist should be aware of.
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Tejido Conectivo/patología , Fibroma Osificante/diagnóstico , Encía/patología , Neoplasias Gingivales/diagnóstico , Maxilar/patología , Enfermedades Maxilares/diagnóstico , Adolescente , Calcinosis , Tejido Conectivo/metabolismo , Femenino , Fibroma Osificante/metabolismo , Fibroma Osificante/patología , Fibrosis , Encía/metabolismo , Neoplasias Gingivales/metabolismo , Neoplasias Gingivales/patología , Gingivitis/diagnóstico , Humanos , Maxilar/metabolismo , Enfermedades Maxilares/metabolismo , Enfermedades Maxilares/patologíaRESUMEN
OBJECTIVE: To investigate the expression of parafibromin in osteosarcoma of the jaws (JOS) and to explore its effects on tumorigenesis and progression. METHODS: The expression of parafibromin was studied in 47 JOS and 11 ossifying fibroma of the jaws (JOF) by immunohistochemically staining. RESULTS: In JOS, the high, medium and low levels of parafibromin expression were detected in 48.9% (23/47), 40.4% (19/47) ,and 10.7% (5/47) of the cases, respectively; correspondingly, the different expressions were seen in 90.9% (10/11), 9.1% (1/11), and 0.0% (0) JOF cases respectively. The difference between JOS and JOF groups was significantly different (U=147.5,P=0.012). In highly differentiated JOS, the expression of parafibromin was significantly higher than that in the conventional JOS (U=71.0,P=0.021) but there were no statistically correlations between the expression of parafibromin and clinical-pathological parameters of JOS (P>0.05). CONCLUSION: It is possible that the down-regulation of parafibromin may be associated with the differentiation and malignant degree of JOS.
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Fibroma Osificante/metabolismo , Neoplasias Maxilomandibulares/metabolismo , Osteosarcoma/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Adulto , Anciano , Regulación hacia Abajo , Femenino , Humanos , Neoplasias Maxilomandibulares/patología , Masculino , Persona de Mediana Edad , Osteosarcoma/patología , Proteínas Supresoras de Tumor/genéticaAsunto(s)
Fibroma Osificante/patología , Neoplasias del Mediastino/patología , Neoplasias de los Tejidos Blandos/patología , Biomarcadores de Tumor/análisis , Femenino , Fibroma Osificante/metabolismo , Humanos , Inmunohistoquímica , Neoplasias del Mediastino/metabolismo , Persona de Mediana Edad , Neoplasias de los Tejidos Blandos/metabolismoRESUMEN
WWOX is a tumour suppressor gene altered in various human neoplasms. Deletion of WWOX is associated with bone metabolic defects and development of osteosarcoma in mice. We hypothesized that alterations of this gene are associated with the development of benign and malignant mesenchymal bone related lesions of the jaws. We investigated WWOX mRNA by nested reverse transcription-PCR and direct sequencing and quantitative real-time PCR in two osteosarcoma, two fibrosarcoma, eight ossifying fibroma and two fibrous dysplasia fresh samples. Malignancy was associated with a decreased WWOX mRNA expression. Aberrant transcription pattern was found in five samples; however, the relative quantification (RQ) of the WWOX mRNA in such lesions was not different from those carrying only the wild-type. We provide new evidence of WWOX alterations in osteosarcomas and demonstrate for the first time alterations of this gene in fibrosarcomas as well as in ossifying fibromas of the jaws.
Asunto(s)
Neoplasias Óseas/genética , Fibroma Osificante/genética , Fibrosarcoma/genética , Neoplasias Maxilomandibulares/genética , Oxidorreductasas/genética , Proteínas Supresoras de Tumor/genética , Adolescente , Adulto , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Niño , Femenino , Fibroma Osificante/metabolismo , Fibroma Osificante/patología , Fibrosarcoma/metabolismo , Fibrosarcoma/patología , Regulación Neoplásica de la Expresión Génica/genética , Genes Supresores de Tumor , Humanos , Neoplasias Maxilomandibulares/metabolismo , Neoplasias Maxilomandibulares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Oxidorreductasas/metabolismo , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Oxidorreductasa que Contiene Dominios WW , Adulto JovenRESUMEN
We have previously established immortalized cells (HCF) from cementifying fibroma of the jaw bone. Here, we found that the receptor for hyaluronan (HA)-mediated motility (RHAMM) and epiregulin, a ligand for the epidermal growth factor receptor (EGFR), were highly expressed in HCF cells in comparison with osteoblasts by conducting a microarray analysis. The cell growth of HCF cells was significantly decreased by the knockdown of RHAMM using small interfering RNA (siRNA). RHAMM was associated with extracellular signal-regulated kinase (ERK) and essential for ERK phosphorylation. HCF cells had characteristic growth mechanisms in which epiregulin functions in an extracellular autocrine loop. Interestingly, exogenous HA induced the phosphorylation of EGFR, which was mainly dependent on CD44. The results raise the novel idea that the EGFR may activate Raf-MEK-ERK signaling in response to the binding of HA to CD44. Moreover, RHAMM was able to associate with TPX2 in the nucleus and was required for HA-induced activation of the Aurora A kinase. The results suggest that RHAMM has a predominant role in the cell cycle in HCF. Here, we report the new machinery by which RHAMM/ERK interaction induces the proliferative activity of cementifying fibroma cells via a specific signaling pathway through the CD44-EGFR axis.
Asunto(s)
Proliferación Celular , Receptores ErbB/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Fibroma Osificante/metabolismo , Receptores de Hialuranos/metabolismo , Aurora Quinasas , Proteínas de Ciclo Celular/metabolismo , Línea Celular Transformada , Núcleo Celular/metabolismo , Activación Enzimática , Factor de Crecimiento Epidérmico/genética , Factor de Crecimiento Epidérmico/metabolismo , Epirregulina , Receptores ErbB/antagonistas & inhibidores , Proteínas de la Matriz Extracelular/genética , Fibroma Osificante/patología , Perfilación de la Expresión Génica , Silenciador del Gen , Humanos , Receptores de Hialuranos/genética , Ácido Hialurónico/metabolismo , Ligandos , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Nucleares/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosforilación , Procesamiento Proteico-Postraduccional , Proteínas Serina-Treonina Quinasas/metabolismo , ARN Mensajero/metabolismo , ARN Interferente Pequeño , Transducción de SeñalAsunto(s)
Dorso/patología , Fibroma Osificante/patología , Neoplasias de los Tejidos Blandos/patología , Anciano , Antígenos CD57/metabolismo , Condrosarcoma/metabolismo , Condrosarcoma/patología , Diagnóstico Diferencial , Fibroma Osificante/metabolismo , Humanos , Masculino , Fosfopiruvato Hidratasa/metabolismo , Proteínas S100/metabolismo , Neoplasias de los Tejidos Blandos/metabolismoAsunto(s)
Fibroma Osificante/patología , Recurrencia Local de Neoplasia/patología , Neoplasias de los Tejidos Blandos/patología , Anciano de 80 o más Años , Diagnóstico Diferencial , Fibroma Osificante/metabolismo , Humanos , Inmunohistoquímica , Masculino , Recurrencia Local de Neoplasia/metabolismo , Neurilemoma/patología , Neoplasias de los Tejidos Blandos/metabolismoRESUMEN
Ossifying fibromyxoid tumor of soft tissues (OFMT) is considered a rare mesenchymal neoplasm. Its main histological features are sheets and ill-defined lobules of rounded bland cells within a fibromyxoid background and a thick collagenous capsule with an incomplete rim of lamellar bone. This lesion occurs mostly in the soft tissues of the lower extremities and limb girdles. In this paper, we describe a mesenchymal tumor removed from the right thigh of a 41 year-old-woman. The neoplasm differed histologically from typical forms of OFMT for areas of moderate cellularity and atypia, nuclear enlargement and small nucleoli. Focally, stromal tongues of osteoid were centrally and irregularly located within the lesion with evident spindling of tumor cells around them. The mitotic activity was low (up to 19 per 50 HPF) and atypical figures were rarely seen. The tumor was positive to S-100 protein, vimentin, CD10, CD56, CD99, ASMA, calponin and collagen IV. Rare elements were positive for cytokeratin AE1/AE3. To the best of our knowledge, this is the first case of atypical OFMT reported to be positive for calponin. The patient is currently alive and well with no evidence of disease at 96 months following surgery. In spite of low-grade histology, OFMT has high local recurrence rate and low metastatic potential, primarily in the lungs, even several years after surgical removal. The recognition of this entity is important. In this report the authors address differential diagnosis and enigmatic histogenesis of this neoplasm.