Promoter Hypermethylation of Tumor Suppressor Genes in Urine from Patients with Cervical Neoplasia

Abstract

We examined the feasibility of using detection of high-risk human papillomavirus (HPV) DNA in combination with the presence of aberrantly methylated genes (DAPK1, RARB, TWIST1, and CDH13 ) for urine-based cervical cancer screening. Urine samples from 129 Senegalese women, aged 35 years or older, 110 with (same day) biopsy-proven cervical neoplasia [cervical intraepithelial neoplasia grade 1 (CIN-1): n = 9; CIN-2 -3/carcinoma in situ (CIS): n = 29; invasive cervical cancer (ICC): n = 72], and 19 without cervical neoplasia on biopsy were examined. Hypermethylation of at least one of the four genes identified 62% of ICC and 28% of CIN-2 -3/CIS and was present in only 4% of CIN-1 or normal urines. High-risk HPV DNA was detected in urine in 70% of those with biopsy-proven ICC, 59% of those with CIN-2 -3/CIS on biopsy, 44% of those with CIN-1 on biopsy, and only 11% of women negative for cervical neoplasia on biopsy. Urine-based detection of either high-risk HPV or hypermethylation of any of the four genes identified 84% of ICC, 64% of CIN-2 -3/CIS, 44% of CIN-1, but only 19% of women negative for cervical neoplasia. The sensitivity for detection of CIN-2 -3/CIS/ICC by high-risk HPV DNA or aberrant DNA methylation of four genes seems to be comparable to that of an exfoliated cervical cytology. This study shows the potential feasibility of using molecular markers detected in urine for cervical cancer screening. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1178 -84)

Aberrant methylation of the PTPRO gene in peripheral blood as a potential biomarker in esophageal squamous cell carcinoma patients

“…Specimen collection should ideally be non-invasive and easily repeatable for monitoring residual or recurrent cancer after treatment. Since hypermethylated DNA may serve as a potential molecular tumor marker due to its high specificity in differentiating cancer from normal tissues, detection of aberrant methylation of tumor suppressor genes in the bodily fluids of cancer patients is attracting increasing attention, for example, in the detection of prostate and cervical cancer from urine, head and neck squamous cell carcinoma by saliva, lung cancer by sputum and bronchial lavage, ovarian cancer by peritoneal fluid, and nasopharyngeal carcinoma by mouth and throat fluid, or nasopharyngeal swab and plasma/serum or blood cells from peripheral blood [22-28]. Among these sample types, the most simple and broadly applicable strategy is to obtain peripheral blood samples from patients.…”

Urine HPV-DNA detection for cervical cancer screening: Prospects and prejudices

“…Although frequency of urine HPV detection increased with increasing severity of the lesion, it was consistently less as compared with that in cervical specimen for each grade of lesion. Feng et al (2007) also demonstrated greater positivity for HPV-DNA in urine samples from patients of invasive cervical cancer (70%), HSIL (59%) and LSIL (44%) as compared with those with no cytological abnormalities (11%). Daponte et al (2006) collected paired samples from 100 consecutive women with abnormal cytology attending the colposcopy clinic.…”

New technologies for cervical cancer screening

“…One study by Feng et. al [35] examined the usage of three methylation biomarkers (DAPK1, RARB, CDH13, and TWIST1) in Senegal, a low-resource setting. These researchers examined the feasibility of using these markers for a urine based cervical cancer screening method.…”