Epigenetic and genetic alternation of PTEN in cervical neoplasm.
OBJECTIVE
We studied the role of epigenetic and genetic changes of PTEN in the development of squamous cell carcinoma (SCC) of the uterine cervix and their value as a prognostic factor.


METHODS
Ten high-grade cervical intraepithelial neoplasia (CIN-H) and 62 SCC tissues were used in this study. Microdissection was performed before loss of PTEN function through methylation of promoter CpG islands, deletion and mutation were studied. The findings were verified with PTEN protein expression and correlated with clinicopathologic information.


RESULTS
PTEN mutation assessed by single-strand conformation polymorphism (PCR-SSCP) was not noted in any of the 62 SCC. Loss of heterozygosity (LOH) was only seen in eight SCC. PTEN promoter methylation was detected in 40% (4/10) of CIN-H and 58% (36/62) of SCC specimens. Loss of PTEN protein expression was associated with methylation of PTEN. PTEN methylation was not related to patient age, tumor grade or stage. Patients with persistent disease or who died of disease had a significantly higher percentage of PTEN methylation than those without evidence of recurrence. Multivariate Cox regression models confirmed PTEN was an important significant predictor both for total and disease-free survival after controlling age, pathologic grade and clinical stage.


CONCLUSIONS
PTEN methylation and loss of PTEN expression are early events in the development of cervical cancer and may have prognostic significance.
Cheung
Tak-Hong
TH
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong. thcheung@cuhk.edu.hk
Lo
Keith Wing-Kit
KW
Yim
So-Fan
SF
Chan
Loucia Kit-Ying
LK
Heung
Mei-Sze
MS
Chan
Chun-Sing
CS
Cheung
Albert Yu-Kiu
AY
Chung
Tony Kwok-Hung
TK
Wong
Yick-Fu
YF
D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D019175:DNA Methylation; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000235:genetics*
D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human