Skip to main content

Advertisement

SpringerLink
Log in

Prognostic Role of Estrogen Receptor α and Estrogen Receptor β in Gastric Cancer

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The presence of estrogen receptor α (ERα) and estrogen receptor β (ERβ) have been reported in cell and tissue level in gastric cancer, but its impact on patients’ survival remains unclear. This study was designed to investigate the expression level of ERα and ERβ and to assess clinical significance of ERα and ERβ expression in gastric cancer.

Methods

The expression level of ERα and ERβ were assessed by reverse-transcriptase polymerase chain reaction (RT-PCR) in 35 surgically resected gastric cancer and corresponding normal tissues and by immunohistochemical staining in 211 surgically resected gastric cancer and match normal tissues.

Results

The expression level between ERα mRNA expression in gastric cancer tissues and match normal tissues had no statistically significant difference. The ERβ mRNA level in normal tissues was significantly higher than that observed in gastric cancer tissues (P = 0.001). Neither ERα nor ERβ mRNA expression levels had significant correlation with clinicopathologic parameters. Forty-eight of 211 (22.7%) gastric cancer tissues showed positive expression of ERα and ERβ detected in gastric cancer. ERα-positive expression correlated with poorer overall survival (P = 0.014), as did the absence of ERβ expression in patients with gastric cancer (P = 0.001). In multivariate analysis, the positive expression of ERα and the absence of ERβ were significant independent prognostic factors for overall survival (hazard ratio 2.159, P = 0.013, and hazard ratio 2.016, P = 0.025 respectively).

Conclusions

Our results indicated that ERα and ERβ were expressed in both gastric cancer and corresponding normal tissues. ERα expression and the absence of ERβ expression are associated with poor survival.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM. Gastric adenocarcinoma: review and considerations for future directions. Ann Surg. 2005;241:27–39.

    PubMed  Google Scholar 

  2. Hohenberger P, Gretschel S. Gastric cancer. Lancet. 2003;362:305–15.

    Article  PubMed  Google Scholar 

  3. Enmark E, Pelto-Huikko M, Grandien K, et al. Human estrogen receptor beta-gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab. 1997;82:4258–65.

    Article  CAS  PubMed  Google Scholar 

  4. Nilsson S, Mäkelä S, Treuter E, et al. Mechanisms of estrogen action. Physiol Rev. 2001;81:1535–65.

    CAS  PubMed  Google Scholar 

  5. Hayashi S, Yamaguchi Y. Estrogen signaling pathway and hormonal therapy. Breast Cancer. 2008;15:256–61.

    Article  PubMed  Google Scholar 

  6. Wigle DT, Turner MC, Gomes J, Parent ME. Role of hormonal and other factors in human prostate cancer. J Toxicol Environ Health B Crit Rev. 2008;11:242–59.

    CAS  PubMed  Google Scholar 

  7. Shen SS, Smith CL, Hsieh JT, et al. Expression of estrogen receptors alpha and beta in bladder cancer cell lines and human bladder tumor tissue. Cancer. 2006;106:2610–16.

    Article  CAS  PubMed  Google Scholar 

  8. Nemenoff RA, Winn RA. Role of nuclear receptors in lung tumourigenesis. Eur J Cancer. 2005;41:2561–8.

    Article  CAS  PubMed  Google Scholar 

  9. Saji S, Kuroi K. Application of selective estrogen receptor modulators for breast cancer treatment according to their intrinsic nature. Breast Cancer. 2008;15:262–9.

    Article  PubMed  Google Scholar 

  10. Lewis-Wambi JS, Jordan VC. Treatment of postmenopausal breast cancer with selective estrogen receptor modulators (SERMs). Breast Dis. 2005–2006;24:93–105.

    Google Scholar 

  11. Hershberger PA, Vasquez AC, Kanterewicz B, Land S, Siegfried JM, Nichols M. Regulation of endogenous gene expression in human non-small cell lung cancer cells by estrogen receptor ligands. Cancer Res. 2005:65:1598–605.

    Article  CAS  PubMed  Google Scholar 

  12. Chandanos E, Rubio CA, Lindblad M, et al. Endogenous estrogen exposure in relation to distribution of histological type and estrogen receptors in gastric adenocarcinoma. Gastric Cancer. 2008;11:168–74.

    Article  CAS  PubMed  Google Scholar 

  13. Pricci M, Linsalata M, Russo F, et al. Effects of 17beta-estradiol administration on apoptosis and polyamine content in AGS cell line. Anticancer Res. 2001;21:3215–20.

    CAS  PubMed  Google Scholar 

  14. Karat D, Brotherick I, Shenton BK, Scott D, Raimes SA, Griffin SM. Expression of oestrogen and progesterone receptors in gastric cancer: a flow cytometric study. Br J Cancer. 1999;80:1271–4.

    Article  CAS  PubMed  Google Scholar 

  15. Singh S, Poulsom R, Wright NA, Sheppard MC, Langman MJ. Differential expression of oestrogen receptor and oestrogen inducible genes in gastric mucosa and cancer. Gut. 1997;40:516–20.

    CAS  PubMed  Google Scholar 

  16. Hogan AM, Collins D, Baird AW, Winter DC. Estrogen and gastrointestinal malignancy. Mol Cell Endocrinol. 2009;307:19–24.

    Article  CAS  PubMed  Google Scholar 

  17. Matsuyama S, Ohkura Y, Eguchi H, et al. Estrogen receptor beta is expressed in human stomach adenocarcinoma. J Cancer Res Clin Oncol. 2002;128:319–24.

    Article  CAS  PubMed  Google Scholar 

  18. Kojima O, Takahashi T, Kawakami S, Uehara Y, Matsui M. Localization of estrogen receptors in gastric cancer using immunohistochemical staining of monoclonal antibody. Cancer. 1991;67:2401–6.

    Article  CAS  PubMed  Google Scholar 

  19. Woo IS, Park MJ, Choi SW et al. Loss of estrogen receptor-alpha expression is associated with hypermethylation near its ATG start codon in gastric cancer cell lines. Oncol Rep. 2004;11:617–22.

    CAS  PubMed  Google Scholar 

  20. Messa C, Russo F, Pricci M, Di Leo A. Epidermal growth factor and 17beta-estradiol effects on proliferation of a human gastric cancer cell line (AGS). Scand J Gastroenterol. 2000;35:753–8.

    Article  CAS  PubMed  Google Scholar 

  21. Takano N, Iizuka N, Hazama S, Yoshino S, Tangoku A, Oka M. Expression of estrogen receptor-alpha and -beta mRNAs in human gastric cancer. Cancer Lett. 2002;176:129–35.

    Article  CAS  PubMed  Google Scholar 

  22. Wang L, Jiang Z, Sui M, Shen J, Xu C, Fan W. The potential biomarkers in predicting pathologic response of breast cancer to three different chemotherapy regimens: a case control study. BMC Cancer. 2009;9:226.

    Article  PubMed  Google Scholar 

  23. Chandanos E, Lagergren J. Oestrogen and the enigmatic male predominance of gastric cancer. Eur J Cancer. 2008;44:2397–403.

    Article  CAS  PubMed  Google Scholar 

  24. Wang M, Pan JY, Song GR, Chen HB, An LJ, Qu SX. Altered expression of estrogen receptor alpha and beta in advanced gastric adenocarcinoma: correlation with prothymosin alpha and clinicopathological parameters. Eur J Surg Oncol. 2007;33:195–201.

    Article  CAS  PubMed  Google Scholar 

  25. Oshima CT, Wonraht DR, Catarino RM, Mattos D, Forones NM. Estrogen and progesterone receptors in gastric and colorectal cancer. Hepatogastroenterology. 1999;46:3155–8.

    CAS  PubMed  Google Scholar 

  26. Ding JX, Feng YJ, Yao LQ, Yu M, Jin HY, Yin LH. The reinforcement of invasion in epithelial ovarian cancer cells by 17 beta-Estradiol is associated with up-regulation of Snail. Gynecol Oncol. 2006;103:623–30.

    Article  CAS  PubMed  Google Scholar 

  27. Park SH, Cheung LW, Wong AS, Leung PC. Estrogen regulates snail and slug in the down-regulation of E-cadherin and induces metastatic potential of ovarian cancer cells through estrogen receptor alpha. Mol Endocrinol. 2008;22:2085–98.

    Article  CAS  PubMed  Google Scholar 

  28. Kousteni S, Bellido T, Plotkin LI, et al. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell. 2001;104:719–30.

    CAS  PubMed  Google Scholar 

  29. Paech K, Webb P, Kuiper GG, Nilsson S, Gustafsson J, Kushner PJ, Scanlan TS. Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites. Science. 1997;277:1508–10.

    Article  CAS  PubMed  Google Scholar 

  30. Maruyama S, Fujimoto N, Asano K, Ito A. Suppression by estrogen receptor beta of AP-1 mediated transactivation through estrogen receptor alpha. J Steroid Biochem Mol Biol. 2001;78:177–84.

    Article  CAS  PubMed  Google Scholar 

  31. Izawa M, Inoue M, Osaki M, Ito H, Harada T, Terakawa N, Ikeguchi M. Cytochrome P450 aromatase gene (CYP19) expression in gastric cancer. Gastric Cancer. 2008;11:103–10.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

Grant support: Zhejiang Science Foundation of China Y208218 (Zhinong jiang).

Author information

Authors and Affiliations

  1. Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China

    C. Y. Xu MD, J. L. Guo MD, Z. N. Jiang MD, S. D. Xie MD, J. G. Shen MD, J. Y. Shen MD & L. B. Wang MD

  2. Sir Run Run Shaw Institute of Clinical Medicine College of Medicine, Zhejiang University, and Key Laboratory of Biotherapy of Zhejiang University, Hangzhou, China

    C. Y. Xu MD, J. L. Guo MD & L. B. Wang MD

  3. Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Z. N. Jiang MD

Authors
  1. C. Y. Xu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. L. Guo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Z. N. Jiang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. D. Xie MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. G. Shen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. Y. Shen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L. B. Wang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. B. Wang MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xu, C.Y., Guo, J.L., Jiang, Z.N. et al. Prognostic Role of Estrogen Receptor α and Estrogen Receptor β in Gastric Cancer. Ann Surg Oncol 17, 2503–2509 (2010). https://doi.org/10.1245/s10434-010-1031-2

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-010-1031-2

Keywords

Search

Navigation