Quantitative analysis of methylation status of the PAX1 gene for detection of cervical cancer

Tien Hung Huang, Hung Chen Lai, Hwan Wun Liu, Cuei Jyuan Lin, Kai Hung Wang, Dah Ching Ding, Tang Yuan Chu

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Objective: Although aided by high-risk human papillomavirus (HPV) DNA test, early detection of cervical cancer is still a challenge. Hypermethylation of the paired boxed gene 1 (PAX1) was recently reported as a characteristic of cervical cancer. This study designed a quantitative measure of PAX1 methylation and compared its efficacy to the currently available Hybrid Capture 2 (HC2) HPV test in detection of cervical cancer. Methods: Using real-time quantitative methylation-specific polymerase chain reaction, we measured the percentage of PAX1 methylation in cervical scrapings obtained from a hospital-based cohort of women with cervical neoplasia of different severities and compared the efficacy of diagnosis of cervical cancer to that of the HC2 HPV test. Results: From 73 cervical scrapings, with diagnoses of normal (n = 17), cervical intra-epithelial neoplasm 1 (CIN1; n = 10), CIN2 (n = 18), CIN3 (n = 14), and invasive cancer (n = 14), the percentage of PAX1 methylation was determined. The percent of methylated reference of invasive cancer (mean [SE], 56.7 [7.1]) was significantly higher than CIN3 (6.5 [2.3]) and the other milder lesions (1.0 [0.3]; P <0.0001). At a cutoff percent of methylated reference value of 4.5, PAX1 methylation was found in 100% of invasive cancer tissue as compared with 0% of normal tissue, 10% of CIN1, 11% of CIN2, and 43% of CIN3 (P <0.0001). As a comparison, the HC2 HPV test result was positive in 5.9% of normal tissue, 70% of CIN1, 55.6% of CIN2, 71.4% of CIN3, and 100% of invasive cancer. In addition to cancer tissue, methylation of PAX1 was also found in normal tissue adjacent to the cancer lesion (9/11, 82%) but much less in the remote normal tissues (2/5, 40%), indicating a field methylation. Conclusions: In this hospital-based study, quantitative measurement of PAX1 hyper-methylation in cervical scrapings is highly sensitive and is more specific than HC2 in detection of cervical cancer.

Original languageEnglish
Pages (from-to)513-519
Number of pages7
JournalInternational Journal of Gynecological Cancer
Volume20
Issue number4
DOIs
Publication statusPublished - May 2010
Externally publishedYes

    Fingerprint

Keywords

  • Cervical cancer
  • DNA methylation
  • Field methylation
  • HPV test
  • PAX1

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology

Cite this