TY - JOUR
T1 - Quantitative analysis of methylation status of the PAX1 gene for detection of cervical cancer
AU - Huang, Tien Hung
AU - Lai, Hung Chen
AU - Liu, Hwan Wun
AU - Lin, Cuei Jyuan
AU - Wang, Kai Hung
AU - Ding, Dah Ching
AU - Chu, Tang Yuan
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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.
KW - Cervical cancer
KW - DNA methylation
KW - Field methylation
KW - HPV test
KW - PAX1
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U2 - 10.1111/IGC.0b013e3181c7fe6e
DO - 10.1111/IGC.0b013e3181c7fe6e
M3 - Article
C2 - 20442585
AN - SCOPUS:77952277597
SN - 1048-891X
VL - 20
SP - 513
EP - 519
JO - International Journal of Gynecological Cancer
JF - International Journal of Gynecological Cancer
IS - 4
ER -
