Evaluation of candidate methylation markers to detect cervical neoplasia.
OBJECTIVE
Studies of cervical cancer and its immediate precursor, cervical intraepithelial neoplasia 3 (CIN3), have identified genes that often show aberrant DNA methylation and therefore represent candidate early detection markers. We used quantitative PCR assays to evaluate methylation in five candidate genes (TNFRSF10C, DAPK1, SOCS3, HS3ST2 and CDH1) previously demonstrated as methylated in cervical cancer.


METHODS
In this analysis, we performed methylation assays for the five candidate genes in 45 invasive cervical cancers, 12 histologically normal cervical specimens, and 23 liquid-based cervical cytology specimens confirmed by expert review as unequivocal demonstrating cytologic high-grade squamous intraepithelial lesions, thus representing the counterparts of histologic CIN3.


RESULTS
We found hypermethylation of HS3ST2 in 93% of cancer tissues and 70% of cytology specimens interpreted as CIN3; hypermethylation of CDH1 was found in 89% of cancers and 26% of CIN3 cytology specimens. Methylation of either HS3ST2 or CDH1 was observed in 100% of cervical cancer tissues and 83% of CIN3 cytology specimens. None of the five genes showed detectable methylation in normal cervical tissues.


CONCLUSIONS
Our data support further evaluation of HS3ST2 and CDH1 methylation as potential markers of cervical cancer and its precursor lesions.
Shivapurkar
Narayan
N
Hamon Center for Therapeutic Oncology Research, Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75930, USA.
Sherman
Mark E
ME
Stastny
Victor
V
Echebiri
Chinyere
C
Rader
Janet S
JS
Nayar
Ritu
R
Bonfiglio
Thomas A
TA
Gazdar
Adi F
AF
Wang
Sophia S
SS
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D016133:Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D005819:Genetic Markers