Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

ESR1 and PGR Gene Promoter Methylation and Correlations with Estrogen and Progesterone Receptors in Ductal and Lobular Breast Cancer

  • Published : 2014.04.01
Download PDF
⟨ Previous Next ⟩

Abstract

The aim of this work was to analyze methylation of the promoter sites of the ESR1 and PGR genes and to determine correlations with immunohistochemical expression of estrogen and progesterone receptors in ductal and lobular breast cancers. An observational, descriptive, molecular study was conducted on 20 ductal and 20 lobular breast cancer samples with immunohistochemical determination of estrogen and progesterone receptor expression. The methylation analysis of ESR1 and PGR promoter sites was carried-out by methylation-specific PCR. For correlation analysis, Kendall's tau coefficient was determined. Positive correlations were found between estrogen and progesterone receptors, estrogen receptor and unmethylated progesterone receptor, progesterone receptor, and unmethylated progesterone receptor. Negative correlations were found between estrogen receptor and methylated progesterone receptor, progesterone receptor and methylated progesterone receptor, methylated and unmethylated estrogen receptor, and methylated and unmethylated progesterone receptor. The results suggest that methylation of promoter sites of ESR1 and PGR is a relatively uncommon event in ductal and lobular breast cancer, and also suggest that the determination of epigenetic states of ESR1 and PGR could represent an alternative or complement to the histopathological expression analysis.

Keywords

References

  1. Allred DC (2010). Issues and updates: evaluating estrogen receptor-alpha, progesterone receptor, and HER2 in breast cancer. Mod Pathol, 23, 52-59. https://doi.org/10.1038/modpathol.2010.55
  2. Baylin SB, Jones PA (2011). A decade of exploring the cancer epigenome-biological and translational implications. Nat Rev Cancer, 11, 726-34. https://doi.org/10.1038/nrc3130
  3. Cancer Genome Atlas Network (2012). Comprehensive molecular portraits of human breast tumours. Nature Oct, 4, 49061-70.
  4. Castoria G, Migliaccio A, Giovannelli P, Auricchio F (2010). Cell proliferation regulated by estradiol receptor: therapeutic implications. Steroids, 75, 524-7. https://doi.org/10.1016/j.steroids.2009.10.007
  5. Esteller M (2008). Epigenetics in cancer. N Engl J Med, 358, 1148-59. https://doi.org/10.1056/NEJMra072067
  6. Feinberg AP, Tycko B (2004). The history of cancer epigenetics. Nat Rev Cancer, 4, 143-53. https://doi.org/10.1038/nrc1279
  7. Gaudet MM, Campan M, Figueroa JD, et al (2009). DNA hypermethylation of ESR1 and PGR in breast cancer: pathologic and epidemiologic associations. Cancer Epidemiol Biomarkers Prev, 18, 3036-43. https://doi.org/10.1158/1055-9965.EPI-09-0678
  8. Goldhirsch A, Winer EP, Coates AS, et al (2013). Personalizing the treatment of women with early breast cancer: highlights of the St gallen international expert consensus on the primary therapy of early breast cancer 2013. Ann Oncol, 24, 2206-23. https://doi.org/10.1093/annonc/mdt303
  9. Hammond ME, Hayes DF, Dowsett M, et al (2010). American society of clinical oncology/college of american pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol, 28, 2784-95. https://doi.org/10.1200/JCO.2009.25.6529
  10. Heichman KA, Warren JD (2012). DNA methylation biomarkers and their utility for solid cancer diagnostics. Clin Chem Lab Me, 50, 1707-21.
  11. Herman JG, Graff JR, Myohanen S, et al (1996) Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA, 93, 9821-6. https://doi.org/10.1073/pnas.93.18.9821
  12. Knutson TP, Lange CA (2013). Tracking progesterone receptor-mediated actions in breast cancer. Pharmacol Ther, [Epub ahead of print].
  13. Lapidus RG, Nass SJ, Butash KA, et al (1998). Mapping of ER gene CpG island methylation-specific polymerase chain reaction. Cancer Res, 58, 2515-9.
  14. Mc Cormack O, Harrison M, Kerin MJ, McCann A (2007). Role of the progesterone receptor (PR) and the PR isoforms in breast cancer. Crit Rev Oncog, 13, 283-301. https://doi.org/10.1615/CritRevOncog.v13.i4.20
  15. Parrella P (2010). Epigenetic signatures in breast cancer: clinical perspective. Breast Care, 5, 66-73. https://doi.org/10.1159/000309138
  16. Purdie CA, Quinlan P, Jordan LB, et al (2014). Progesterone receptor expression is an independent prognostic variable in early breast cancer: a population-based study. Br J Cancer, 110, 565-72. https://doi.org/10.1038/bjc.2013.756
  17. Radisky DC, Bissell MJ (2007). NF-kappaB links oestrogen receptor signalling and EMT. Nat Cell Biol, 9, 361-3. https://doi.org/10.1038/ncb0407-361
  18. Ramezani F, Salami S, Omrani MD, Maleki D (2012). CpG island methylation profile of estrogen receptor alpha in Iranian females with triple negative or non-triple negative breast cancer: new marker of poor prognosis. Asian Pac J Cancer Prev, 13, 451-7. https://doi.org/10.7314/APJCP.2012.13.2.451
  19. Renoir JM, Marsaud V, Lazennec G (2013). Estrogen receptor signaling as a target for novel breast cancer therapeutics. Biochem Pharmacol, 85, 449-65. https://doi.org/10.1016/j.bcp.2012.10.018
  20. Sasaki M, Dharia A, Oh BR, et al (2001). Progesterone receptor B gene inactivation and CpG hypermethylation in human uterine endometrial cancer. Cancer Res, 61, 97-102.
  21. Sturgeon SR, Balasubramanian R, Schairer C, et al (2012). Detection of promoter methylation of tumor suppressor genes in serum DNA of breast cancer cases and benign breast disease controls. Epigenetics, 7, 1258-67. https://doi.org/10.4161/epi.22220
  22. Wessa P (2011) Free statistics software, office for research development and education, version 1.23-r7, available in www.wessa.net/.).

Cited by

  1. Overexpression of Hiwi Promotes Growth of Human Breast Cancer Cells vol.15, pp.18, 2014, https://doi.org/10.7314/APJCP.2014.15.18.7553
  2. Hypermethylation of CDKN2A exon 2 in tumor, tumor-adjacent and tumor-distant tissues from breast cancer patients vol.17, pp.1, 2017, https://doi.org/10.1186/s12885-017-3244-2
  3. Gene in Breast Tissue of Healthy Women: A Missing Link with Breast Cancer Risk Factors? vol.21, pp.8, 2017, https://doi.org/10.1089/gtmb.2017.0028
  4. ESR1-promoter-methylation status in primary breast cancer and its corresponding metastases pp.1573-7276, 2018, https://doi.org/10.1007/s10585-018-9935-5