Assessing the contribution of HRPT2 to the pathogenesis of jaw fibrous dysplasia, ossifying fibroma, and osteosarcoma

Netto, Ana Carolina de Mesquita; Gomez, Ricardo Santiago; Diniz, Marina Gonçalves; Fonseca–Silva, Thiago; Campos, Kelma; Marco, Luiz; Carlos, Román; Gomes, Carolina Cavaliéri

doi:10.1016/j.oooo.2012.11.015

Cited by 28 publications

(12 citation statements)

References 29 publications

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“…31 Isolated cytogenetic abnormalities have been reported in rare cases but no recurrent genetic modification. [32][33][34][35] Zhang et al recently suggested that modified Notch signaling (Notch being involved in the control of cell Table 3 Comparison of the presence of MDM2 and RASAL1 amplifications in fibrous dysplasia, juvenile ossifying fibromas and nonjuvenile (conventional) ossifying fibromas…”

Section: Discussionmentioning

confidence: 99%

Chromosome 12 long arm rearrangement covering MDM2 and RASAL1 is associated with aggressive craniofacial juvenile ossifying fibroma and extracranial psammomatoid fibro-osseous lesions

et al. 2015

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To evaluate the diagnostic value of MDM2 status in craniofacial fibro-osseous lesions, we investigated MDM2 expression by immunohistochemistry and analyzed MDM2 amplification by qPCR in 30 cases of ossifying fibroma (including 13 cases of the juvenile variant) and 17 cases of fibrous dysplasia. Two cases of uncommon extragnathic psammomatoid fibrous dysplasia and a mixed control group of 15 cases of low-grade osteosarcoma and 15 cases of well-differentiated/dedifferentiated liposarcoma were included. MDM2 amplification was found in 33% of ossifying fibromas (peak of 69% for the juvenile variant) and in 12% of fibrous dysplasia, in none of which was MDM2 overexpressed. All control cases exhibited MDM2 amplification and overexpression. To investigate possible polysomy of chromosome 12, we studied RASAL1 amplification, a gene telomeric to MDM2 on the long arm of chromosome 12. RASAL1 amplification was reported in all benign fibro-osseous lesions exhibiting MDM2 amplification but not in controls. Simultaneous amplification of these two genes was significantly higher in juvenile ossifying fibromas compared with fibrous dysplasia (P ¼ 0.004), non-juvenile ossifying fibromas (P ¼ 0.001), and all other benign craniofacial fibro-osseous lesions combined (P ¼ 0.0001). Of the nine cases of juvenile ossifying fibroma exhibiting amplification, three were locally invasive and four were recurrent, suggesting aggressive disease. The two cases of extragnathic psammomatoid fibrous dysplasia also showed MDM2 and RASAL1 amplification with no MDM2 overexpression. This large chromosome 12 rearrangement, spanning MDM2 and RASAL1, is the first recurrent molecular abnormality to be reported in juvenile ossifying fibroma. It may represent both a molecular diagnostic marker and a characteristic of more aggressive forms with a higher risk of recurrence. Finally, the presence of this rearrangement in extragnathic psammomatoid fibro-osseous lesions mimicking ossifying fibromas might reflect a common molecular pathway in their pathogenesis and calls into question the classification of such lesions within fibrous dysplasia.

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Section: Discussionmentioning

confidence: 99%

Chromosome 12 long arm rearrangement covering MDM2 and RASAL1 is associated with aggressive craniofacial juvenile ossifying fibroma and extracranial psammomatoid fibro-osseous lesions

et al. 2015

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“…The restricted sample size was a limitation of this study. However, the rarity and limited number of FDs of the jaws make it challenging to design studies in this field [16,40]. Only one study in which three centers have collaborated had sufficient cases of FD and OF of the jaws [6], therefore, multicenter studies to obtain a larger sample size, is recommended.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and Biological Significance of Immunohistochemical Expression of Osteopontin and Ki67 in Fibro-osseous lesions of jaws

Sargolzaei

Ghelejkhani²,

Baghban

2017

J Islam Dent Assoc Iran

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Background and Aim: Fibrous dysplasia (FD) and ossifying fibroma (OF) are the most important fibro-osseous lesions (FOLs) of the jaws with similarities in radiographic and morphological features while showing completely different biological behavior. Limited studies have been evaluated immunohistochemistry markers, such as osteopontin (OPN) and osteocalcin to help differentiate these two lesions. This study aimed to assess the immunoexpression of OPN and Ki67 as potential markers for differentiation of different FOLs. Materials and Methods: This cross-sectional study was conducted on 12 FD, 19 OF, and eight FOL samples retrieved from the archives of the department of oral pathology. The specimens were examined immunohistochemically using streptavidin-biotin method for OPN and Ki67. The intensity score (IS), proportional score (PS) and total score (TS) were assessed in hard and soft tissue matrix and in mesenchymal cells for Ki67. The data were analyzed by independent samples Kruskal-Wallis. Results: Osteopontin showed positive immunoreaction in both stromal and trabecular components of all FDs and OFs. Among the scores, PS and TS of bone trabeculae were significantly different in FD and OF (P=0.005). Nevertheless, no significant difference was observed in Ki67 expression in mesenchymal cells (P=0.880) and OPN scores in soft tissue matrix between the lesions; their P-value were 0.336, 0.340 and 0.415 for IS, TS, and PS, respectively. Conclusion: Osteopontin can serve as a useful marker for differential diagnosis of FD and OF. However, we suggest evaluation of other NCMPs, especially functionally similar molecules such as bone sialoproteins (BSPs) in FOLs for differential diagnosis.

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“…LOH analysis was done as previously reported. 10 Briefly, the ratio between short-allele/long-allele (reference tissue) and short-allele/long allele (tumor) was calculated. Ratio values <0.66 or >1.5 were interpreted as LOH.…”

Section: Loss Of Heterozygosity Analysismentioning

confidence: 99%

Loss of heterozygosity of MIR15A/MIR16-1, negative regulators of the antiapoptotic gene BCL2, is not common in odontogenic keratocysts

Resende

Bernardes

Silva

et al. 2018

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

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Assessing the contribution of HRPT2 to the pathogenesis of jaw fibrous dysplasia, ossifying fibroma, and osteosarcoma

Abstract: The contribution of HRPT2 inactivation to the pathogenesis of OF, FD, and OS is marginal at best and may be limited to progression rather than tumor initiation.

Cited by 28 publications

References 29 publications

Chromosome 12 long arm rearrangement covering MDM2 and RASAL1 is associated with aggressive craniofacial juvenile ossifying fibroma and extracranial psammomatoid fibro-osseous lesions

Chromosome 12 long arm rearrangement covering MDM2 and RASAL1 is associated with aggressive craniofacial juvenile ossifying fibroma and extracranial psammomatoid fibro-osseous lesions

Diagnostic and Biological Significance of Immunohistochemical Expression of Osteopontin and Ki67 in Fibro-osseous lesions of jaws

Loss of heterozygosity of MIR15A/MIR16-1, negative regulators of the antiapoptotic gene BCL2, is not common in odontogenic keratocysts

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