Loss of FANCD2 and related proteins may predict malignant transformation in oral epithelial dysplasia.
Oral Surg Oral Med Oral Pathol Oral Radiol
; 133(4): 377-387, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-34493474
ABSTRACT
OBJECTIVE:
Predicting malignant transformation (MT) in oral epithelial dysplasia (OED) is challenging. The higher rate of MT reported in nonsmokers suggests an endogenous etiology in oncogenesis. We hypothesize that loss of FANCD2 and associated proteins could influence genomic instability and MT in the absence of environmental carcinogens. STUDYDESIGN:
Longitudinal archival samples were obtained from 40 individuals with OED from diagnosis to the most recent review in 23 patients with stable OED or until excision of the squamous cell carcinoma in 17 patients with unstable OED undergoing MT. Histopathological reassessment, immunohistochemistry for FANCD2, and Western blotting for phosphorylation/monoubiquitylation status of ATR, CHK1, FANCD2, and FANCG were undertaken on each tissue sample.RESULTS:
Decreased expression of FANCD2 was observed in the diagnostic biopsies of OED lesions that later underwent MT. Combining the FANCD2 expression scores with histologic grading more accurately predicted MT (P = .005) than histology alone, and it correctly predicted MT in 10 of 17 initial biopsies. Significantly reduced expression of total FANCD2, pFANCD2, pATR, pCHK-1, and pFANCG was observed in unstable OED.CONCLUSIONS:
There is preliminary evidence that defects in the DNA damage sensing/signaling/repair cascade are associated with MT in OED. Loss of expression of FANCD2 protein in association with a higher histologic grade of dysplasia offered better prediction of MT than clinicopathologic parameters alone.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesões Pré-Cancerosas
/
Neoplasias Bucais
/
Carcinoma de Células Escamosas
/
Proteína do Grupo de Complementação D2 da Anemia de Fanconi
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Oral Surg Oral Med Oral Pathol Oral Radiol
Ano de publicação:
2022
Tipo de documento:
Article