Estrogen receptor α and β in esophageal squamous cell carcinoma

Cancer Sci. 2012 Jul;103(7):1348-55. doi: 10.1111/j.1349-7006.2012.02288.x. Epub 2012 May 15.

Abstract

A gender difference has been reported in the morbidity of esophageal squamous cell carcinoma (ESCC). Estrogens have been proposed to play a role in this difference but the details have not yet been clarified. Therefore, in the present study, we examined the status of estrogen receptor (ER)α and ERβ in 90 Japanese ESCC patients. ERα and ERβ immunoreactivity was detected in the nuclei of ESCC cells (41.1 and 97.8%, respectively). There was a significant positive association between the ERβ H score and histological differentiation (P = 0.0403), TNM-pM (LYM) (P = 0.00164) and Ki67/MIB1 LI of carcinoma cells (P = 0.0497, r = 0.207). In addition, the ERβ status of carcinoma cells was significantly correlated with unfavorable clinical outcome of the patients. Multivariate analysis further revealed the ERβ status in carcinoma cells as an independent unfavorable prognostic factor of these patients. We further examined the effects of estrogen treatment on ESCC cell line (ECGI-10) transfected with ERα or ERβ in vitro. The number of ECGI-10 transfected with ERβ was increased by estradiol or ERβ specific agonist but estradiol did not exert any effect upon the cell number of ECGI-10 transfected with ERα. In summary, the results of the present study clearly demonstrate that the status of ERβ in ESCC was closely associated with the unfavorable prognosis, possibly through altering cell proliferation of carcinoma cells.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism*
  • Estrogen Receptor beta / genetics
  • Estrogen Receptor beta / metabolism*
  • Estrogens / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Phenols
  • Prognosis
  • Pyrazoles / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens
  • Ki-67 Antigen
  • Phenols
  • Pyrazoles
  • 4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol
  • Estradiol