Abstract
PCDH10 is a member of the protocadherin cell adhesion molecule family, which are frequently downregulated in cancers. This study aimed to characterize the methylation silencing of the PCDH10 gene in the full spectrum of cervical carcinogenesis and to clarify if a field effect of methylation might be a target for a diagnostic test from cervical scrapings. Methylation silencing of PCDH10 was found in four of five cervical cancers and one of two cervical precancerous cell lines, which could be reversed by demethylation treatment. The same methylation was detected in 85.7% (24/28) of invasive cancer tissues, 36.4% (4/11) of high-grade squamous intraepithelial lesions, 20% (1/5) of low-grade squamous intraepithelial lesions, and none (0/17) of the normal cervical tissues from non-cancer subjects. In addition, methylation was also frequently found in histologically 'normal' cervical tissues adjacent to cancer lesions (7/13, 53.8%) and, less frequently, in vaginal and endometrial tissues (1/8, 12.5%). Further investigation of cervical scrapings revealed cancer-specific methylation of PCDH10 with a methylation rate of 71% (22/31) in invasive cancer, 27.9% (12/43) in carcinoma in situ, and none in high-grade squamous intraepithelial lesions excluding carcinoma in situ (n = 12), low-grade squamous intraepithelial lesions (n = 27), and normal controls (n = 66) (P < 10(-16)). Compared to the high-risk human papilloma virus test, PCDH10 methylation testing of cervical scrapings was more specific (92 vs 60%) but less sensitive (71 vs 96%) in detecting invasive cervical cancer. This study demonstrated field methylation of the PCDH10 gene specifically in the invasion stage of cervical carcinogenesis, which might be used to develop a highly specific diagnostic test for cervical scrapings.