Significance of p53-binding protein 1 nuclear foci in uterine cervical lesions: endogenous DNA double strand breaks and genomic instability during carcinogenesis.
Histopathology
; 59(3): 441-51, 2011 Sep.
Article
en En
| MEDLINE
| ID: mdl-22034884
ABSTRACT
AIMS:
A defective DNA damage response can result in genomic instability (GIN) and lead to transformation to cancer. As p53-binding protein 1 (53BP1) localizes at the sites of DNA double strand breaks (DSBs) and rapidly forms nuclear foci (NF), the presence of 53BP1 NF can be considered to be an indicator of endogenous DSBs reflecting GIN. Our aim was to analyse the presence of DSBs by immunofluorescence for 53BP1 expression in a series of cervical lesions, to evaluate the significance of GIN during carcinogenesis. METHODS ANDRESULTS:
A total of 80 archival cervical tissue samples, including 11 normal, 16 cervical intraepithelial neoplasia (CIN)1, 15 CIN2, 24 CIN3 and 14 squamous cell carcinoma samples, were analysed for 53BP1 NF, human papillomavirus (HPV) infection, and p16(INK4a) overexpression. The number of 53BP1 NF in cervical cells appeared to increase with progression during carcinogenesis. The distribution of 53BP1 NF was similar to that of the punctate HPV signals as determined by in-situ hybridization and also to p16(INK4a) overexpression in CIN, suggesting an association with viral infection and replication stress.CONCLUSIONS:
Immunofluorescence analysis of 53BP1 expression can be a useful tool with which to estimate the level of GIN. During cervical carcinogenesis, GIN may allow further accumulation of genomic alterations, causing progression to invasive cancer.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Carcinoma de Células Escamosas
/
Transformación Celular Neoplásica
/
Neoplasias del Cuello Uterino
/
Inestabilidad Genómica
/
Péptidos y Proteínas de Señalización Intracelular
/
Roturas del ADN de Doble Cadena
Límite:
Female
/
Humans
Idioma:
En
Revista:
Histopathology
Año:
2011
Tipo del documento:
Article
País de afiliación:
Japón