Skip to main content

Advertisement

SpringerLink
Log in

Expression and Prognostic Value of Oestrogen Receptor Beta in Colorectal Cancer

  • Original Article
  • Published:
Pathology & Oncology Research

Abstract

Differences between men and women in the incidence and biological mechanisms of colorectal cancer (CRC) suggest that estrogens may play a role in the pathogenesis of this disease. The identification of the human estrogen receptor beta (ERβ) and its expression in the intestinal mucosa led to further studies that revealed that estrogens have a protective function against CRC mediated by the activation of ERβ. However, ERβ expression and its role in CRC is controversial. The purpose of this study was to determine the distribution and prognostic value of ERβ expression in the intestinal mucosa of patients diagnosed and surgically treated for CRC, and its association with other known prognostic factors. A total of 109 paraffin-embedded samples of the wild-type ERβ isoform were analyzed by immunohistochemical nuclear staining in patients with colorectal adenocarcinoma. Clinical/pathological and survival data were collected. Immunohistochemical quantification was performed using the category scoring system, which has been validated for assessing estrogen receptor alfa. The wild-type ERβ isoform –also called ERβ1– was positive in 101 patients (92.7%) and negative in nine patients (7.3%). Univariate analysis revealed that the absence of expression of the ERβ1 gene was correlated with mucinous adenocarcinoma (p < 0.05). Also, a non-significant tendency was observed for ERβ expression to be down-regulated in advanced tumors. With a median follow-up of 47 months, the overall survival and progression-free survival were not found to be associated with ERβ1 expression (p = 0.2). Although the wild-type ERβ isoform was expressed in most study patients with colorectal cancer, it does not seem to have any prognostic value for the course of the disease. Further studies should be conducted to investigate whether the down-regulation of ERβ expression has any biological function in mucinous colorectal cancer.

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

Similar content being viewed by others

References

  1. Siegel R, Naishadham D, Jemal A (2013) Cancer statistics. CA Cancer J Clin 63:11–30

    Article  PubMed  Google Scholar 

  2. Sánchez MJ, Payer T, de Angelis R, Larrañaga R, Capocaccia R, Martinez C, CIBERESP working group (2010) Cancer incidence and mortality in Spain: estimates and projections for the period 1981–2012. Ann Oncol 21:30–36

    Article  Google Scholar 

  3. Howe HL, Wu X, Ries LA, Cokkinides V, Ahmed F, Jemal A et al (2006) Annual report to the nation on the status of cancer, 1975–2003, featuring cancer among U.S. Hispanic/Latino populations. Cancer 107:1711

    Article  PubMed  Google Scholar 

  4. Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA (1996) Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A 93:5925–5930

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Mosselman S, Polman J, Dijkema R (1996) ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett 392:49–53

    Article  PubMed  CAS  Google Scholar 

  6. Moore JT, Mckee DD, Slentz-Kesler K, Moore LB, Jones SA, Horne EL et al (1998) Cloning and characterization of human estrogen receptor beta isoforms. Biochem Biophys Res Commun 247:75–78

    Article  PubMed  CAS  Google Scholar 

  7. Hasson RM, Briggs A, Carothers AM, Davids JS, Wang J, Javid SH et al (2014) Estrogen receptor alfa or beta loss in the colon of min/+ mice promotes crypt expansion and impairs TGFbeta and HNF3beta signaling. Carinogenesis 35:96–102

    Article  CAS  Google Scholar 

  8. Barone M, Tanzi S, Lofano K, Scavo MP, Pricci M, Demarinis L et al (2010) Dietaryy-induced ERbeta upregulation counteracts intestinal neoplasia development in intact male ApcMin/+ mice. Carcinogenesis 31:269–274

    Article  PubMed  CAS  Google Scholar 

  9. Calle EE, Miracle-Mahill HL, Thun MJ, Heath CW Jr (1995) Estrogen replacement therapy and risk of fatal colon cancer in a prospective cohort of postmenopausical women. J Nat Cancer Inst 87:517–523

    Article  PubMed  CAS  Google Scholar 

  10. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML et al (2002) Risk and benefits of estrogen plus progestin in healthy postmenopausal women: principal result from the Women’s health initiative randomized controlled trial. JAMA 288:321–333

    Article  PubMed  CAS  Google Scholar 

  11. Rudolph A, Toth C, Hoffmeister M, Roth W, Herpel E, Schirmacher P et al (2013) Colorectal cancer risk associated with hormone use varies by expression of estrogen receptor-beta. Cancer Res 73:3306–3315

    Article  PubMed  CAS  Google Scholar 

  12. Jassam N, Bell SM, Speirs V, Quirke P (2005) Loss of expression of oestrogen receptor β in colon cancer and its association with dukes` staging. Oncol Rep 14:17–21

    PubMed  CAS  Google Scholar 

  13. Fang YJ, Lu ZH, Wang F, Wu XJ, Li LR, Zhang LY et al (2010) Prognostic impact of ERβ and MMP7 expression on overall survival in colon cancer. Tumor Biol 31:651–658

    Article  CAS  Google Scholar 

  14. Reproducido con permiso del AJCC: Greene FL, Page PL, Fleming ID, et al. AJCC Cancer Staging Manual 6th ed. New York: Springer-Verlag, 2002

  15. Grivas PD, Tzelepi V, Sotiropoulou-Bonikou G, Kefalopoulou Z, Papavassiliou AG, Kalofonos H (2009) Expression of ERβ, ER alpha and co-regulator PELP1/MNAR in colorectal cancer: prognosis significance and clinopathologic correlations. Cell Oncol 31:235–247

    PubMed  PubMed Central  CAS  Google Scholar 

  16. Elbanna HG, Ebrahim MA, Abbas AM, Zalata K, Hashim MA (2012) Potential value of estrogen receptor beta expression in colorectal carcinoma: interaction with apoptotic index. J Gastrointest Cancer 43:56–62

    Article  PubMed  CAS  Google Scholar 

  17. Harvey JM, Clark GM, Osborne CK, Allred DC (1999) Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 17:1474–1481

    Article  PubMed  CAS  Google Scholar 

  18. Xie LQ, Yu JP, Luo HS (2004) Expression of estrogen receptor β in human colorectal cancer. Word J Gastroenterol 10:214–217

    Article  CAS  Google Scholar 

  19. Campbell-Thompson M, Lynch J, Bhardwaj B (2001) Expression of estrogen receptor subtypes and Erβ isoforms in colon cancer. Cancer Res 61:632–640

    PubMed  CAS  Google Scholar 

  20. Taggarshe D, Lobocki C, Silberberg B, McKendrick A, Mittal VK (2012) Clinicopathological significance of the expression of estrogen receptor-beta and vascular endotelial growth factor-a in colorectal cancer. Am Surg 78:1376–1382

    PubMed  Google Scholar 

  21. Rudolph A, Toth C, Hoffmeister M, Roth W, Herpel E, Jansen L et al (2012) Expresion of oestrogen receptor β and prognosis of colorectal cancer. Br J Cancer 107:831–839

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Rath-Wolfson L, Purim O, Ram E, Morgenstern S, Koren R, Brenner B. Expression of estrogen receptor β1 in colorectal cancer: correlation with clinicopathological variables. Oncology Reports 27:2017–2022

  23. Konstantinopoulos PA, Kominea A, Vandoros G, Sykiotis GP, Andricopoulos P, Varakis I et al (2003) Oestrogen receptor beta is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour’s dedifferentiation. Eur J Cancer 39:1251–1258

    Article  PubMed  CAS  Google Scholar 

  24. Castiglione F, Taddei A, DeglÍnnocenti R, Buccoliero AM, Bechi P, Garbini F et al (2008) Expression of estrogen receptor β in colon cancer progression. Diagn Mol Pathol 17:231–236

    Article  PubMed  CAS  Google Scholar 

  25. Wong NA, Malcomson RD, Jodrell DI, Groome NP, Harrison DJ (2005) Saunders PT.ERbeta isoform expression in colorectal carcinomas:an in vivo and in vitro study of clinicapathological and molecular correlates. J Pathol 207:53–60

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was funded by the Andalusian Oncology Society (SAC).

Author information

Authors and Affiliations

  1. Division of Medical Oncology, Hospital Virgen de la Victoria, Malaga, Spain

    Elisabeth Pérez-Ruiz, Esperanza Torres, Isabel Sevilla, Emilio Alba & Lorenzo Alonso

  2. Division of Medical Oncology, Hospital Costa del Sol, Marbella, Spain

    Elisabeth Pérez-Ruiz & Antonio Rueda

  3. Red de Investigación en Servicios de Salud (REDISSEC), Marbella, Spain

    Elisabeth Pérez-Ruiz, Antonio Rueda, Francisco Rivas-Ruiz, Maximino Redondo & Maria Padilla-Ruiz

  4. Patology Deparment, Hospital Hospital Virgen de la Victoria, Malaga, Spain

    Lidia Pérez, Vanesa de Luque & Martina Álvarez

  5. Research Unit, Hospital Costa del Sol, Marbella, Spain

    Francisco Rivas-Ruiz, Maximino Redondo & Maria Padilla-Ruiz

Authors
  1. Elisabeth Pérez-Ruiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonio Rueda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lidia Pérez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francisco Rivas-Ruiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Esperanza Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vanesa de Luque
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Martina Álvarez
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Isabel Sevilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Maximino Redondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Maria Padilla-Ruiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Emilio Alba
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Lorenzo Alonso
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elisabeth Pérez-Ruiz.

Ethics declarations

This study was performed in compliance with the principles of the Declaration of Helsinki (Seul 2008). Informed consent was obtained from all participants. This study was approved by the Ethics Committee of the Virgen de la Victoria Hospital, Malaga, Spain, where the study was performed.

Conflict of Interests

The authors have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pérez-Ruiz, E., Rueda, A., Pérez, L. et al. Expression and Prognostic Value of Oestrogen Receptor Beta in Colorectal Cancer. Pathol. Oncol. Res. 24, 871–879 (2018). https://doi.org/10.1007/s12253-017-0301-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-017-0301-8

Keywords

Search

Navigation