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Breast Cancer Research and Treatment

, Volume 111, Issue 1, pp 45–53 | Cite as

Progesterone receptor B (PRB) promoter hypermethylation in sporadic breast cancer

Progesterone receptor B hypermethylation in breast cancer
  • Orla Mc CormackEmail author
  • Wen Y. Chung
  • Patricia Fitzpatrick
  • Fiachra Cooke
  • Barbara Flynn
  • Michele Harrison
  • Edward Fox
  • Emma Gallagher
  • Aloysius McGoldrick
  • Peter A. Dervan
  • Amanda McCann
  • Michael J. Kerin
Preclinical Study

Abstract

Introduction Oestrogen receptor alpha (ER alpha) is traditionally measured on all breast tumour specimens to identify those patients more likely to respond to anti-oestrogens. Progesterone receptor (PR) status has contributed useful information in defining more responsive subgroups. PR negativity may be a marker for increased signalling through growth factor receptor tyrosine kinase pathways. Progesterone acts through two PRs, PRA and PRB. PRB, the functionally active PR, can be silenced by promoter hypermethylation. Methods Following DNA and RNA extraction from 94 breast carcinomas, the methylation status of the PRB promoter was assessed by sodium bisulphite modification and methylation sensitive PCR (MSP). A quantitative realtime PCR analysis (QRTPCR) was used to determine the levels of PRB mRNA expression. Protein expression was evaluated immunohistochemically with a commercially available PRB antibody. Results 76% of the primary breast carcinoma samples demonstrated a methylated band for PRB. PRB methylation significantly compromised total PR immunohistochemistry (IHC) expression (= 0.03). PRB mRNA correlated positively with total PR IHC (= 0.58, = 0.04), ER alpha IHC (= 0.02), and tumour grade (P = 0.01). PRB protein expression was significantly associated with a number of favourable prognostic variables including smaller (P = 0.004) lower grade (= 0.007), ER alpha IHC positive tumours (< 0.001), and tumours with a low Nottingham Prognostic Index (NPI) (P = 0.0008). PRB mRNA levels were significantly associated with better overall survival (= 0.04) in a univariate analysis. Conclusion The majority of tumours were methylated for PRB. This did not directly compromise PRB expression suggesting that other factors may down regulate the PR gene. When PRB was expressed, it correlated with good prognostic markers and better overall survival.

Keywords

Breast cancer Immunohistochemistry Epigenetics Oestrogen receptor alpha Progesterone receptor B Promoter hypermethylation 

Notes

Acknowledgement

The present study was supported by a Mater Research Grant.

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Copyright information

© Springer Science+Business Media, LLC. 2007

Authors and Affiliations

  • Orla Mc Cormack
    • 1
    Email author
  • Wen Y. Chung
    • 2
  • Patricia Fitzpatrick
    • 3
  • Fiachra Cooke
    • 2
  • Barbara Flynn
    • 2
  • Michele Harrison
    • 4
  • Edward Fox
    • 2
  • Emma Gallagher
    • 2
  • Aloysius McGoldrick
    • 2
  • Peter A. Dervan
    • 4
  • Amanda McCann
    • 2
  • Michael J. Kerin
    • 5
  1. 1.The Adelaide and Meath Hospital, Dublin Incorporating the National Childrens HospitalDublinIreland
  2. 2.UCD School of Medicine and Medical Science (SMMS), UCD Conway InstituteDublin 4Ireland
  3. 3.UCD School of Public Health and Population ScienceDublin 4Ireland
  4. 4.Department of PathologyMater Misericordiae HospitalDublin 7Ireland
  5. 5.Clinical Science InstituteUniversity College HospitalGalwayIreland

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