Decreased expression of the CDK inhibitor p27Kip1 and increased oxidative DNA damage in the multistep process of cervical carcinogenesis.
OBJECTIVE
The expression of the CDK inhibitor p27Kip1 and the extent of endogenous oxidative DNA damage were evaluated in the multistep cervical carcinogenesis.


METHODS
Archival specimens of low-grade (L) squamous intraepithelial lesions (SILs) (n=32), high-grade (H) SILs (n=24) and invasive carcinomas (n=48) of the cervix were included in the analysis compared with normal cervical squamous epithelium (n=15). Expression level of p27Kip1 was evaluated by immunostaining. Immunohistochemical detection of 8-hydroxydeoxyguanosine (8-OHdG) was considered as marker of oxidative DNA damage in the same tissues.


RESULTS
p27Kip1 was constantly expressed in normal epithelium with a mean percentage of positive cells higher than 50%. A progressive significant reduction in the mean percentage of positive cells was observed in L-SIL (18.1%), H-SIL (7.3%) and in invasive carcinomas (2.5%). A progressive significant increase in the levels of 8-OHdG and in the percentage of mean positive cells was observed from L-SIL (2.2%) to H-SIL (12.5%) to invasive carcinomas (25.2%). p27Kip1 and 8-OHdG expression displayed a significant inverse relationship.


CONCLUSIONS
Expression of p27Kip1 is down-regulated while oxidative DNA damage increases during cervical carcinogenesis. Both parameters are altered at early stages of the process and might help to predict patients at high risk of progression.
Centro di Ricerche Oncologiche Giovanni XXIII, Istituto di Anatomia Patologica, Università Cattolica del Sacro Cuore, Rome, Italy. asgambato@rm.unicatt.it
Alessandro
A
Sgambato
Gian Franco
GF
Zannoni
Beatrice
B
Faraglia
Andrea
A
Camerini
Elisabetta
E
Tarquini
Daniele
D
Spada
Achille
A
Cittadini
D000080242:8-Hydroxy-2'-Deoxyguanosine; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004249:DNA Damage / Q000502:physiology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018384:Oxidative Stress / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine