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Progesterone receptor B (PRB) promoter hypermethylation in sporadic breast cancer: progesterone receptor B hypermethylation in breast cancer.
Breast Cancer Res Treat. 2008 Sep; 111(1):45-53.BC

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 (P = 0.03). PRB mRNA correlated positively with total PR IHC (r = 0.58, P = 0.04), ER alpha IHC (P = 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 (P = 0.007), ER alpha IHC positive tumours (P < 0.001), and tumours with a low Nottingham Prognostic Index (NPI) (P = 0.0008). PRB mRNA levels were significantly associated with better overall survival (P = 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.

Authors+Show Affiliations

The Adelaide and Meath Hospital, Dublin Incorporating the National Childrens Hospital, Tallaght, Dublin, 24, Ireland. omccormack@rcsi.ieNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17896177

Citation

Mc Cormack, Orla, et al. "Progesterone Receptor B (PRB) Promoter Hypermethylation in Sporadic Breast Cancer: Progesterone Receptor B Hypermethylation in Breast Cancer." Breast Cancer Research and Treatment, vol. 111, no. 1, 2008, pp. 45-53.
Mc Cormack O, Chung WY, Fitzpatrick P, et al. Progesterone receptor B (PRB) promoter hypermethylation in sporadic breast cancer: progesterone receptor B hypermethylation in breast cancer. Breast Cancer Res Treat. 2008;111(1):45-53.
Mc Cormack, O., Chung, W. Y., Fitzpatrick, P., Cooke, F., Flynn, B., Harrison, M., Fox, E., Gallagher, E., McGoldrick, A., Dervan, P. A., McCann, A., & Kerin, M. J. (2008). Progesterone receptor B (PRB) promoter hypermethylation in sporadic breast cancer: progesterone receptor B hypermethylation in breast cancer. Breast Cancer Research and Treatment, 111(1), 45-53.
Mc Cormack O, et al. Progesterone Receptor B (PRB) Promoter Hypermethylation in Sporadic Breast Cancer: Progesterone Receptor B Hypermethylation in Breast Cancer. Breast Cancer Res Treat. 2008;111(1):45-53. PubMed PMID: 17896177.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Progesterone receptor B (PRB) promoter hypermethylation in sporadic breast cancer: progesterone receptor B hypermethylation in breast cancer. AU - Mc Cormack,Orla, AU - Chung,Wen Y, AU - Fitzpatrick,Patricia, AU - Cooke,Fiachra, AU - Flynn,Barbara, AU - Harrison,Michele, AU - Fox,Edward, AU - Gallagher,Emma, AU - McGoldrick,Aloysius, AU - Dervan,Peter A, AU - McCann,Amanda, AU - Kerin,Michael J, Y1 - 2007/09/26/ PY - 2007/09/05/received PY - 2007/09/10/accepted PY - 2007/9/27/pubmed PY - 2008/9/17/medline PY - 2007/9/27/entrez SP - 45 EP - 53 JF - Breast cancer research and treatment JO - Breast Cancer Res Treat VL - 111 IS - 1 N2 - 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 (P = 0.03). PRB mRNA correlated positively with total PR IHC (r = 0.58, P = 0.04), ER alpha IHC (P = 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 (P = 0.007), ER alpha IHC positive tumours (P < 0.001), and tumours with a low Nottingham Prognostic Index (NPI) (P = 0.0008). PRB mRNA levels were significantly associated with better overall survival (P = 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. SN - 0167-6806 UR - https://www.unboundmedicine.com/medline/citation/17896177/Progesterone_receptor_B__PRB__promoter_hypermethylation_in_sporadic_breast_cancer:_progesterone_receptor_B_hypermethylation_in_breast_cancer_ L2 - https://doi.org/10.1007/s10549-007-9757-7 DB - PRIME DP - Unbound Medicine ER -