DOI QR코드

DOI QR Code

PAX1 Methylation Analysis by MS-HRM is Useful in Triage of High-grade Squamous Intraepithelial Lesions

  • Wang, Zhen-Ming (Department of Clinical Laboratory, Weifang City People's Hospital)
  • Published : 2014.01.30

Abstract

This study is aimed to investigate the role of paired boxed gene 1 (PAX1) methylation analysis by methylation-sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and compared its performance with the Hybrid Capture 2 (HC2) human papillomavirus (HPV) test. In our study, 130 cases with a diagnosis of ASC-H from the cervical cytological screening by Thinprep cytologic test (TCT) technique were selected for triage. Their cervical scrapings were collected and evaluated by using PAX1 methylation analysis (MS-HRM) and high-risk HPV DNA test (HC2), followed by colposcopy and cervical biopsy. Chi-square test were used to test the differences of PAX1 methylation or HPV infection between groups. In the detection of CIN2+, the sensitivity, specificity, the PPV, NPV and the accuracy of PAX1 MS-HRM assay and high-risk HPV (HR-HPV) tests were respectively 80.6% vs 67.7%, 94.9% vs 54.5%, 83.3%, vs 31.8%, 94.0% vs 84.4%, and 91.5% vs 57.7%. The PAX1 MS-HRM assay proved superior to HR-HPV testing in the detection of high grade lesions (CIN2+) in ASC-H. This approach could screen out the majority of high grade lesion cases of ASC-H, and thus could reduce the referral rate to colposcopy.

Keywords

References

  1. Bandyopadhyay S, Austin RM, Dabbs D, Zhao C (2008). Adjunctive human papillomavirus DNA testing is a useful option in some clinical settings for disease risk assessment and triage of females with ASC-H Papanicolaou test results. Arch Pathol Lab Med, 132, 1874-81.
  2. Candiloro IL, Mikeska T, Dobrovic A (2011). Assessing combined methylation-sensitive high resolution melting and pyrosequencing for the analysis of heterogeneous DNA methylation. Epigenetics, 6, 500-7. https://doi.org/10.4161/epi.6.4.14853
  3. Carreon JD, Sherman ME, Guillen D, et al (2007). CIN2 is a much less reproducible and less valid diagnosis than CIN3: results from a histological review of population-based cervical samples. Int J Gynecol Pathol, 26, 441-6. https://doi.org/10.1097/pgp.0b013e31805152ab
  4. Dimitrakopoulos L, Vorkas PA, Georgoulias V, Lianidou ES (2012). A closed-tube methylation-sensitive high resolution melting assay (MS-HRMA) for the semi-quantitative determination of CST6 promoter methylation in clinical samples. BMC Cancer, 12, 486. https://doi.org/10.1186/1471-2407-12-486
  5. Kristensen LS, Wojdacz TK, Thestrup BB, et al (2009). Quality assessment of DNA derived from up to 30 years old formalin fixed paraffin embedded (FFPE) tissue for PCR-based methylation analysis using SMART-MSP and MS-HRM. BMC Cancer, 9, 453. https://doi.org/10.1186/1471-2407-9-453
  6. Lai HC, Lin YW, Huang TH, et al (2008). Identification of novel DNA methylation markers in cervical cancer. Int J Cancer, 123, 161-7. https://doi.org/10.1002/ijc.23519
  7. Nambaru L, Meenakumari B, Swaminathan R, Rajkumar T (2009). Prognostic significance of HPV physical status and integration sites in cervical cancer. Asian Pac J Cancer Prev, 10, 355-60.
  8. Selvaggi SM (2013). Clinical significance of atypical squamous cells cannot exclude high grade squamous intraepithelial lesion with histologic correlation-: A 9-Year experience. Diagn Cytopathol, 41, 943-6. https://doi.org/10.1002/dc.22982
  9. Sherman ME, Castle PE, Solomon D (2006). Cervical cytology of atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H): characteristics and histologic outcomes. Cancer, 108, 298-305. https://doi.org/10.1002/cncr.21844
  10. Sherman ME, Solomon D, Schiffman M (2001). Qualification of ASCUS. A comparison of equivocal LSIL and equivocal HSIL cervical cytology in the ASCUS LSIL Triage Study. Am J Clin Pathol, 116, 386-94. https://doi.org/10.1309/JM3V-U4HP-W8HJ-68XV
  11. The ASCUS-LSIL Triage Study (ALTS) Group (2003). Results of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance. Am J Obstet Gynecol, 188, 1383-92. https://doi.org/10.1016/S0002-9378(03)00418-6
  12. Walboomers JM, Jacobs MV, Manos MM, et al (1999). Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol, 189, 12-9. https://doi.org/10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F
  13. Wang JL, Yang YZ, Dong WW, et al (2013). Application of human papillomavirus in screening for cervical cancer and precancerous lesions. Asian Pac J Cancer Prev, 14, 2979-82. https://doi.org/10.7314/APJCP.2013.14.5.2979
  14. Wittwer CT, Reed GH, Gundry CN, Vandersteen JG, Pryor RJ (2003). High-resolution genotyping by amplicon melting analysis using LCGreen. Clin Chem, 49, 853-60. https://doi.org/10.1373/49.6.853
  15. Wojdacz TK, Dobrovic A (2007). Methylation-sensitive high resolution melting (MS-HRM): a new approach for sensitive and high-throughput assessment of methylation. Nucleic Acids Res, 35, e41. https://doi.org/10.1093/nar/gkm013
  16. Wright TC, Jr., Cox JT, Massad LS, Twiggs LB, Wilkinson EJ (2002). 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities. JAMA, 287, 2120-9. https://doi.org/10.1001/jama.287.16.2120
  17. Wu HH, Allen SL, Kirkpatrick JL, Elsheikh TM (2006). Reflex high-risk human papilloma virus DNA test is useful in the triage of women with atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion. Diagn Cytopathol, 34, 707-10. https://doi.org/10.1002/dc.20497
  18. Wu W, Zhang J, Yang H, Shao Y, Yu B (2011). Examination of AKAP12 promoter methylation in skin cancer using methylation-sensitive high-resolution melting analysis. Clin Exp Dermatol, 36, 381-5. https://doi.org/10.1111/j.1365-2230.2010.03968.x

Cited by

  1. C13orf18 and C1orf166 (MULAN) DNA Genes Methylation are Not Associated with Cervical Cancer and Precancerous Lesions of Human Papillomavirus Genotypes in Iranian Women vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6745
  2. CCNA1 Promoter Methylation: a Potential Marker for Grading Papanicolaou Smear Cervical Squamous Intraepithelial Lesions vol.15, pp.18, 2014, https://doi.org/10.7314/APJCP.2014.15.18.7971
  3. Triage of ASC-H: A meta-analysis of the accuracy of high-risk HPV testing and other markers to detect cervical precancer vol.124, pp.4, 2015, https://doi.org/10.1002/cncy.21661
  4. Clinical application of a rapid cervical cancer screening method: Folate receptor-mediated staining of cervical neoplastic epithelia vol.13, pp.1, 2016, https://doi.org/10.1111/ajco.12573
  5. Methylation of Cervical Neoplastic Cells Infected With Human Papillomavirus 16 vol.26, pp.1, 2016, https://doi.org/10.1097/IGC.0000000000000582
  6. PAX1 Methylation as a Potential Biomarker to Predict the Progression of Cervical Intraepithelial Neoplasia vol.27, pp.7, 2017, https://doi.org/10.1097/IGC.0000000000001011
  7. ) gene methylation in cancer screening pp.23249269, 2019, https://doi.org/10.1002/mgg3.506