Altered expression of estrogen receptor alpha and beta in advanced gastric adenocarcinoma: correlation with prothymosin alpha and clinicopathological parameters

Eur J Surg Oncol. 2007 Mar;33(2):195-201. doi: 10.1016/j.ejso.2006.09.009. Epub 2006 Oct 13.

Abstract

Aims: We aimed to investigate the sources of estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta) and estimate the value of both ER subtypes in gastric adenocarcinoma and analyze the possible relationship of prothymosin alpha (ProTalpha) to ERs.

Methods: ERs at the mRNA and protein levels in matched advanced gastric adenocarcinomas and surrounding non-cancerous tissues were examined by using reverse transcription-polymerase chain reaction and immunohistochemical (IHC) methods. Cell proliferation related protein ProTalpha was also detected in IHC. The immunoreactive signal, corresponding to the proteins expression level, was quantitatively analyzed.

Results: Both ERalpha and ERbeta mRNAs were detected in most of the cancer and matched normal tissues analyzed. At the protein level, the percentage of ERalpha and ERbeta positive cases changed. ERalpha immunoreactivity was only detected in poorly differentiated adenocarcinoma and ERalpha positive expression correlated with depth of invasion of the tumors. Compared with non-cancerous tissues, gastric tumors showed decreased ERbeta expression and lost ERbeta. Altered ERbeta in gastric adenocarcinoma correlated with decreased differentiation. And the tumors involved lymph node metastasis showed significantly lower expression level of ERbeta. ProTalpha in ERbeta-positive tumors showed higher expression than that in lost ERbeta tumors.

Conclusions: Altered expression of ERalpha and ERbeta in tumors compared with corresponding normal gastric tissues was more common in poorly differentiated adenocarcinomas and related to malignant properties, such as lymph node metastasis. Decreased ERbeta and increased ProTalpha expression in advanced gastric adenocarcinoma indicated that ERbeta may play an anti-proliferation role which is opposed to the role of ProTalpha in gastric epithelium.

MeSH terms

  • Adenocarcinoma* / genetics
  • Adenocarcinoma* / metabolism
  • Adenocarcinoma* / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Cell Differentiation
  • Estrogen Receptor alpha / biosynthesis
  • Estrogen Receptor alpha / genetics*
  • Estrogen Receptor beta / biosynthesis
  • Estrogen Receptor beta / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Protein Precursors / biosynthesis
  • Protein Precursors / genetics*
  • RNA, Neoplasm / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Severity of Illness Index
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / metabolism
  • Stomach Neoplasms* / pathology
  • Thymosin / analogs & derivatives*
  • Thymosin / biosynthesis
  • Thymosin / genetics

Substances

  • Biomarkers, Tumor
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Protein Precursors
  • RNA, Neoplasm
  • prothymosin alpha
  • Thymosin