Gadd45a levels in human breast cancer are hormone receptor dependent

J Transl Med. 2013 May 24;11:131. doi: 10.1186/1479-5876-11-131.

Abstract

Background: Gadd45a is a member of the Gadd45 family of genes that are known stress sensors. Gadd45a has been shown to serve as an effector in oncogenic stress in breast carcinogenesis in murine models. The present study was aimed at clarifying the expression of Gadd45a in human breast cancer and its correlation with clinicopathologic features.

Methods: The expression levels of Gadd45a in breast tissue samples of female breast surgery cases were examined by immunohistochemistry (IHC) using a Gadd45a antibody. Percent staining was determined and statistical analyses were applied to determine prognostic correlations.

Results: 56 female breast surgery cases were studied: Normal (11), Luminal A (9), Luminal B (11), HER2+ (10), Triple Negative (15). There was a highly significant difference in percent Gadd45a staining between groups [Mean]: Normal 16.3%; Luminal A 65.3%; Luminal B 80.7%; HER2+ 40.5%; TN 32%, P < 0.001, ANOVA. Gadd45a IHC levels for Normal cases found 82% negative/low. Luminal A breast cancer cases were found to be 67% high. Luminal B breast cancers were 100% high. Her2+ cases were 50% negative/low. Triple Negative cases were 67% negative/low. This difference in distribution of Gadd45a levels across breast cancer receptor subtypes was significant, P = 0.0009.

Conclusions: Gadd45a levels are significantly associated with hormone receptor status in human breast cancer. Normal breast tissue displays low Gadd45a levels. High Gadd45a levels are associated with Luminal A and Luminal B subtypes. Absence of hormone receptors in Triple Negative subtype is associated with Negative/Low levels of Gadd45a. Further studies are indicated to elucidate the role of Gadd45a in breast cancer as a potential prognosticator or target for treatment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biomarkers, Tumor / metabolism
  • Breast / metabolism
  • Breast Neoplasms / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Nuclear Proteins / metabolism*
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Triple Negative Breast Neoplasms / metabolism

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • GADD45A protein, human
  • Nuclear Proteins
  • ERBB2 protein, human
  • Receptor, ErbB-2