Alterations in the expression of DNA damage response-related molecules in potentially preneoplastic oral epithelial lesions

Nikitakis, Nikolaos G.; Rassidakis, George Z.; Tasoulas, Jason; Gkouveris, Ioannis; Kamperos, Georgios; Daskalopoulos, Argyriοs; Sklavounou, Alexandra

doi:10.1016/j.oooo.2018.03.006

Cited by 14 publications

(21 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The direct evaluation of the DNA sensing-signalling-damage repair cascade in OED has not been previously reported, although there is recent evidence that individuals with reduced, systemic, double strand break repair capacity are more prone develop to head and neck cancer (38). It has been suggested that activation of DNA damage response might be protective in the early stages of oral carcinogenesis, but progressive deregulation over time could eventually result in the failure to suppress malignant transformation (41). The results of the current study indicate that additional evaluation of these pathways is worthwhile to understand their capability to predict malignant transformation in OED at the initial diagnostic biopsy, especially as time to transformation may be as long as 7 years (1,3).…”

Section: Discussionmentioning

confidence: 99%

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

Ryan

Gupta

et al. 2022

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Ryan

Gupta

et al. 2022

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

View full text Add to dashboard Cite

show abstract

“…Wild-type p53 protein is expressed in < 5% of basal cells in normal epithelium [40]. Its expression is increased in OED although the degree of expression varied in studies by different studies [40][41][42]. However, if there is continuous positivity within > 90% of basal cell nuclei and in suprabasal nuclei, this is very strongly associated with the dysplastic phenotype; it is also strongly expressed in SCC.…”

Section: Keratosis Of Uncertain Significance (Kus)mentioning

confidence: 99%

Oral Epithelial Dysplasia and Premalignancy

Woo

2019

Head and Neck Pathol

103

View full text Add to dashboard Cite

Leukoplakia and erythroplakia are two entities under the moniker of "oral potentially malignant disorders" that are highly associated with the presence of oral epithelial dysplasia (OED) at first biopsy, while lesions of submucous fibrosis develop OED after being present for years. Importantly, traumatic/frictional keratoses are often mistaken clinically for leukoplakia and it is important for the pathologist to recognize and report them as such. The features of OED have been well-described and other architectural features will be discussed here, in particular verrucous and papillary architecture, bulky epithelial proliferation and epithelial atrophy. Proliferative leukoplakia, verrucous or otherwise, often show only hyperkeratosis in early lesions, with development of OED occurring over time, and squamous cell carcinoma developing in the majority of cases over time. The concept of hyperkeratosis without features of OED and that is not reactive, is likely a precursor to the dysplastic phenotype. Many cases of leukoplakia exhibiting OED are associated with a band of lymphocytes at the interface and these should not be mistaken for oral lichen planus.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Ryan

Gupta

et al. 2020

Preprint

View full text Add to dashboard Cite

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.

show abstract

Alterations in the expression of DNA damage response-related molecules in potentially preneoplastic oral epithelial lesions

Cited by 14 publications

References 61 publications

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

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

Oral Epithelial Dysplasia and Premalignancy

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

Contact Info

Product

Resources

About