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Breast Cancer Research and Treatment

, Volume 100, Issue 2, pp 169–176 | Cite as

Association of GSTP1 CpG Islands Hypermethylation with Poor Prognosis in Human Breast Cancers

  • Takashi Arai
  • Yasuo Miyoshi
  • Seung Jin Kim
  • Tetsuya Taguchi
  • Yasuhiro Tamaki
  • Shinzaburo NoguchiEmail author
Clinical Trial

Abstract

Glutathione S-transferase P1 (GSTP1) belongs to a family of phase II metabolic enzymes that can detoxify the carcinogens and cytotoxic drugs by conjugating them with glutathione. Relationship of GSTP1 CpG islands hypermethylation or GSTP1 protein expression with clinicopathological characteristics of breast cancers was studied. The CpG islands hypermethylation status of GSTP1 gene was studied by methylation specific primer assay and GSTP1 expression was studied by immunohistochemistry in primary breast cancers. Of 174 breast tumors, 24 (14%) were found to have GSTP1 CpG islands hypermethylation. A significant association was found between GSTP1 CpG islands hypermethylation and large tumor size (P < 0.01) or lymph node metastases (P < 0.05). Relapse-free survival (RFS) rates of patients with GSTP1 CpG islands hypermethylation were significantly poorer than those without it (5-year RFS rates; 60 vs. 86%, P < 0.01). Multivariate analysis showed that GSTP1 CpG islands hypermethylation status was a statistically significant prognostic factor being independent of other conventional prognostic factors. Immunohistochemical study showed that here was a significant association between GSTP1 CpG islands hypermethylation and loss of GSTP1 expression (P < 0.01) but that RFS rates of patients with GSTP1 positive tumors were not significantly different from those with GSTP1 negative tumors. GSTP1 CpG islands hypermethylation, but not GSTP1 protein expression, is associated with a poor prognosis of breast cancers, suggesting that GSTP1 CpG islands hypermethylation has a potential to serve as a clinically useful prognostic factor.

Key words

GSTP1 Hypermethylation Breast cancer Prognosis 

Abbreviations

LN

Lymph node

ER

Estrogen receptor

PgR

Progesterone receptor

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Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Takashi Arai
    • 1
  • Yasuo Miyoshi
    • 1
  • Seung Jin Kim
    • 1
  • Tetsuya Taguchi
    • 1
  • Yasuhiro Tamaki
    • 1
  • Shinzaburo Noguchi
    • 1
    Email author
  1. 1.Department of Surgical OncologyOsaka University Graduate School of MedicineOsakaJapan

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