Loss of FANCD2 and related proteins may predict malignant transformation in oral epithelial dysplasia

Abstract Background: Predicting malignant transformation in oral epithelial dysplasia(OED) is a clinical challenge. The higher rate of malignant transformation in non-smokers supports an endogenous aetiology. Loss of FANCD2 and associated proteins could lead to genomic instability and oncogenesis.Methods: Longitudinal archival samples from 40 individuals with OED from time of diagnosis to the most recent review in 23 stable OED; or until excision of the SCC in 17 unstable OED undergoing malignant transformation. Histopathological reassessment, immunohistochemistry for FANCD2 and Western blotting for phosphorylation/monubiquitination status of ATR, CHK1, FANCD2 and FANCG were undertaken on each tissue sample.Results: Decreased expression of FANCD2 was observed in the diagnostic biopsy of OED lesions which later underwent malignant transformation. Combining the FANCD2 expression scores with histological grading more accurately predicted malignant transformation (p=0.005) than histology alone and correctly predicted malignant transformation in 10/17 initial biopsies. Significantly reduced expression of total FANCD2, pFANCD2, pATR, pCHK-1 and pFANCG were observed in unstable OED.Discussion: There is good evidence that defects in the DNA damage sensing-signalling-repair cascade are associated with malignant transformation in OED. Loss of post-translational modification in FANCD2 and related proteins, was more predictive of malignant transformation when compared to clinicopathological parameters.

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Loss of FANCD2 and related proteins may predict malignant transformation in oral epithelial dysplasia

10.21203/rs.2.17496/v3 ◽

2020 ◽

Author(s):

Michael W Ho ◽

Mark Ryan ◽

Juhi Gupta ◽

Asterios Triantafyllou ◽

Janet Risk ◽

...

Keyword(s):

Malignant Transformation ◽

Tissue Sample ◽

Good Evidence ◽

Epithelial Dysplasia ◽

Clinicopathological Parameters ◽

Post Translational Modification ◽

Oral Epithelial Dysplasia ◽

Damage Sensing ◽

Related Proteins ◽

Oral Epithelial

Abstract Background: Predicting malignant transformation in oral epithelial dysplasia(OED) is a clinical challenge. The higher rate of malignant transformation in non-smokers supports an endogenous aetiology. Loss of FANCD2 and associated proteins could lead to genomic instability and oncogenesis. Patients & Methods: Longitudinal archival samples from 40 individuals with OED from time of diagnosis to the most recent review in 23 stable OED; or until excision of the SCC in 17 unstable OED undergoing malignant transformation. Histopathological reassessment, immunohistochemistry for FANCD2 and Western blotting for phosphorylation/monubiquitination status of ATR, CHK1, FANCD2 and FANCG were undertaken on each tissue sample. Results: Decreased expression of FANCD2 was observed in the diagnostic biopsy of OED lesions which later underwent malignant transformation. Combining the FANCD2 expression scores with histological grading more accurately predicted malignant transformation (p=0.005) than histology alone and correctly predicted malignant transformation in 10/17 initial biopsies. Significantly reduced expression of total FANCD2, pFANCD2, pATR, pCHK-1 and pFANCG were observed in unstable OED. Discussion: There is good evidence that defects in the DNA damage sensing-signalling-repair cascade are associated with malignant transformation in OED. Loss of post-translational modification in FANCD2 and related proteins, was more predictive of malignant transformation when compared to clinicopathological parameters.

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Loss of FANCD2 and related proteins may predict malignant transformation in oral epithelial dysplasia

10.21203/rs.2.17496/v5 ◽

2020 ◽

Author(s):

Michael W Ho ◽

Mark Ryan ◽

Juhi Gupta ◽

Asterios Triantafyllou ◽

Janet Risk ◽

...

Keyword(s):

Malignant Transformation ◽

Tissue Sample ◽

Good Evidence ◽

Epithelial Dysplasia ◽

Clinicopathological Parameters ◽

Post Translational Modification ◽

Oral Epithelial Dysplasia ◽

Damage Sensing ◽

Related Proteins ◽

Oral Epithelial

Abstract Background: Predicting malignant transformation in oral epithelial dysplasia(OED) is a clinical challenge. The higher rate of malignant transformation in non-smokers supports an endogenous aetiology. Loss of FANCD2 and associated proteins could lead to genomic instability and oncogenesis. Methods: Longitudinal archival samples from 40 individuals with OED from time of diagnosis to the most recent review in 23 stable OED; or until excision of the SCC in 17 unstable OED undergoing malignant transformation. Histopathological reassessment, immunohistochemistry for FANCD2 and Western blotting for phosphorylation/monubiquitination status of ATR, CHK1, FANCD2 and FANCG were undertaken on each tissue sample. Results: Decreased expression of FANCD2 was observed in the diagnostic biopsy of OED lesions which later underwent malignant transformation. Combining the FANCD2 expression scores with histological grading more accurately predicted malignant transformation (p=0.005) than histology alone and correctly predicted malignant transformation in 10/17 initial biopsies. Significantly reduced expression of total FANCD2, pFANCD2, pATR, pCHK-1 and pFANCG were observed in unstable OED. Discussion: There is good evidence that defects in the DNA damage sensing-signalling-repair cascade are associated with malignant transformation in OED. Loss of post-translational modification in FANCD2 and related proteins, was more predictive of malignant transformation when compared to clinicopathological parameters.

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Loss of FANCD2 and related proteins may predict malignant transformation in oral epithelial dysplasia

10.21203/rs.2.17496/v1 ◽

2019 ◽

Author(s):

Michael W Ho ◽

Mark Ryan ◽

Juhi Gupta ◽

Asterios Triantafyllou ◽

Janet Risk ◽

...

Keyword(s):

Malignant Transformation ◽

Tissue Sample ◽

Good Evidence ◽

Epithelial Dysplasia ◽

Clinicopathological Parameters ◽

Post Translational Modification ◽

Oral Epithelial Dysplasia ◽

Damage Sensing ◽

Related Proteins ◽

Oral Epithelial

Abstract Background: Predicting malignant transformation in oral epithelial dysplasia(OED) is a clinical challenge. The higher rate of malignant transformation in non-smokers supports an endogenous aetiology. Loss of FANCD2 and associated proteins could lead to genomic instability and oncogenesis. Patients & Methods: Longitudinal archival samples from 40 individuals with OED from time of diagnosis to the most recent review in 23 stable OED; or until excision of the SCC in 17 unstable OED undergoing malignant transformation. Histopathological reassessment, immunohistochemistry for FANCD2 and Western blotting for phosphorylation/monubiquitination status of ATR, CHK1, FANCD2 and FANCG were undertaken on each tissue sample. Results:Decreased expression of FANCD2 was observed in the diagnostic biopsy of OED lesions which later underwent malignant transformation. Combining the FANCD2 expression scores with histological grading more accurately predicted malignant transformation (p=0.005) than histology alone and correctly predicted malignant transformation in 10/17 initial biopsies. Significantly reduced expression of total FANCD2, pFANCD2, pATR, pCHK-1 and pFANCG were observed in unstable OED. Discussion: There is good evidence that defects in the DNA damage sensing-signalling-repair cascade are associated with malignant transformation in OED. Loss of post-translational modification in FANCD2 and related proteins, was more predictive of malignant transformation when compared to clinicopathological parameters.

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Loss of FANCD2 and related proteins may predict malignant transformation in oral epithelial dysplasia

10.21203/rs.2.17496/v6 ◽

2020 ◽

Author(s):

Michael W Ho ◽

Mark Ryan ◽

Juhi Gupta ◽

Asterios Triantafyllou ◽

Janet Risk ◽

...

Keyword(s):

Malignant Transformation ◽

Tissue Sample ◽

Good Evidence ◽

Epithelial Dysplasia ◽

Clinicopathological Parameters ◽

Post Translational Modification ◽

Oral Epithelial Dysplasia ◽

Damage Sensing ◽

Related Proteins ◽

Oral Epithelial

Abstract Background: Predicting malignant transformation in oral epithelial dysplasia(OED) is a clinical challenge. The higher rate of malignant transformation in non-smokers supports an endogenous aetiology. Loss of FANCD2 and associated proteins could lead to genomic instability and oncogenesis. Methods: Longitudinal archival samples from 40 individuals with OED from time of diagnosis to the most recent review in 23 stable OED; or until excision of the SCC in 17 unstable OED undergoing malignant transformation. Histopathological reassessment, immunohistochemistry for FANCD2 and Western blotting for phosphorylation/monubiquitination status of ATR, CHK1, FANCD2 and FANCG were undertaken on each tissue sample. Results: Decreased expression of FANCD2 was observed in the diagnostic biopsy of OED lesions which later underwent malignant transformation. Combining the FANCD2 expression scores with histological grading more accurately predicted malignant transformation (p=0.005) than histology alone and correctly predicted malignant transformation in 10/17 initial biopsies. Significantly reduced expression of total FANCD2, pFANCD2, pATR, pCHK-1 and pFANCG were observed in unstable OED. Discussion: There is good evidence that defects in the DNA damage sensing-signalling-repair cascade are associated with malignant transformation in OED. Loss of post-translational modification in FANCD2 and related proteins, was more predictive of malignant transformation when compared to clinicopathological parameters.

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Loss of FANCD2 and related proteins may predict malignant transformation in oral epithelial dysplasia

Oral Surgery Oral Medicine Oral Pathology and Oral Radiology ◽

10.1016/j.oooo.2021.07.001 ◽

2021 ◽

Author(s):

Michael W Ho ◽

Mark P Ryan ◽

Juhi Gupta ◽

Asterios Triantafyllou ◽

Janet M Risk ◽

...

Keyword(s):

Malignant Transformation ◽

Epithelial Dysplasia ◽

Oral Epithelial Dysplasia ◽

Related Proteins ◽

Oral Epithelial

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Malignant Transformation Rate in Patients Presenting Oral Epithelial Dysplasia: Systematic Review and Meta-Analysis

Journal of Oral Diseases ◽

10.1155/2015/854636 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Jaffer A. Shariff ◽

Athanasios I. Zavras

Keyword(s):

Systematic Review ◽

Malignant Transformation ◽

Observational Studies ◽

Meta Analysis ◽

Epithelial Dysplasia ◽

High Rate ◽

Transformation Rate ◽

Oral Epithelial Dysplasia ◽

Observational Cohort ◽

Oral Epithelial

Objective. To perform a systematic review and meta-analysis on studies that assess malignant transformation rates (MTR) of oral epithelial dysplasia. Materials and Methods. This review was planned and conducted in accordance with the meta-analysis of observational studies in epidemiology (MOOSE) guidelines. PubMed, EMBASE, Google Scholar, and Cochrane databases were screened to identify observational studies. Quality assessments were completed by two reviewers independently using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Pooled-malignant transformation rate (MTR) in person years, subgroup, sensitivity, and publication bias analysis were calculated using STATA 13.0 and Comprehensive Meta-Analysis software. Results. Sixteen observational cohort studies were identified with a total of 3708 participants from Asia, North America, and Europe. Analysis showed a MTR of 10.5% (pooled-MTR: 10.5, 95% CI: 3.7 to 17.3; fixed effect model, I2=0.0%; Q-value = 2.389; p>0.05) among patients with histologically confirmed oral epithelia dysplasia undergoing long-term follow-up. Higher MTR in person year were seen among the sever dysplastic cases (pooled-MTR: 14.4%, 95% CI: 5.3% to 23.5%), studies published in Europe (pooled-MTR: 12.6%, 95% CI: 8.0% to 24.3%), and retrospective studies (pooled-MTR: 11.0%, 95% CI: 2.2% to 19.9%). Conclusion. These studies show that oral epithelial dysplasia has a significant high rate of transformation to cancer.

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