Skip to main content

Advertisement

Log in

Prognostic significance of HE4 expression in pulmonary adenocarcinoma

  • Research Article
  • Published:
Tumor Biology

Abstract

We investigated the possibility of human epididymis 4(HE4) to predict survival for patients with pulmonary adenocarcinoma. One hundred and thirty-seven patients with pulmonary adenocarcinoma underwent surgery in our institute from 2000 to 2008. We used immunohistochemical analysis to determine the expression of HE4 and compared with the clinicopathological factors and survival. Serum levels of HE4 in lung adenocarcinoma were investigated by enzyme immunometric assay. Fifty-seven of 137 cases (41.6%) were HE4 positive. It was found that there was no correlation between HE4 expression by immunohistochemistry and clinicopathological factors, however, adenocarcinoma subtype was significantly associated with HE4 expression. Sera in lung adenocarcinoma were significantly higher than in healthy control. Five-year disease-free survival in the HE4-positive group (44.6%) was significantly different from that in the negative group (82.3%, p = 0.001) by immunohistochemistry. The five-year overall survival rate was 60.1% in the HE4-positive group, as compared with 90.8% in the HE4-negative group (p = 0.001). In multivariate Cox regression analysis, positive HE4 protein expression was a worse prognosis factor of disease-free and overall survival (HR = 3.7, 95%CI = [1.7–8.4], p = 0.001; HR = 5.5, 95%CI = [1.8–17.2], p = 0.003, respectively), in addition to nodal status as a powerful value. When HE4 expression in adenocarcinoma cases except the BAC were analyzed, nodal status and HE4 expression were independent prognostic factors in disease-free and overall survivals. These data showed that HE4 expression is associated with a worse prognosis and is a possible prognostic factor of lung adenocarcinoma.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997;111:1710–7.

    Article  CAS  PubMed  Google Scholar 

  2. Pass HI, Carbone DP, Johnson DH, Minna JD, ScagliottiGV, Turrisi III AT (2009) Principles and practice of lung cancer, 4th edn. Lippincott Williams & Wilkins, Philadelphia

  3. Bingle L, Singleton V, Bingle CD. The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms. Oncogene. 2002;21:2768–73.

    Article  CAS  PubMed  Google Scholar 

  4. Wiedow O, Schröder JM, Gregory H, Young JA, Christophers E. Elafin: an elastase-specific inhibitor of human skin. Purification, characterization, and complete amino acid sequence. J Biol Chem. 1990;265:14791–5.

    CAS  PubMed  Google Scholar 

  5. Thompson RC, Ohlsson K. Isolation, properties, and complete amino acid sequence of human secretory leukocyte protease inhibitor, a potent inhibitor of leukocyte elastase. Proc Natl Acad Sci USA. 1986;83:6692–6.

    Article  CAS  PubMed  Google Scholar 

  6. Schummer M, Ng WV, Bumgarner RE, Nelson PS, Schummer B, Bednarski DW, et al. Comparative hybridization of an array of 21, 500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas. Gene. 1999;238:375–85.

    Article  CAS  PubMed  Google Scholar 

  7. Hellström I, Raycraft J, Hayden-Ledbetter M, Ledbetter JA, Schummer M, McIntosh M, et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res. 2003;63:3695–700.

    PubMed  Google Scholar 

  8. Anastasi E, Granato T, Marchei GG, Viggiani V, Colaprisca B, Comploj S, et al. Ovarian tumor marker HE4 is differently expressed during the phases of the menstrual cycle in healthy young women. Tumour Biol. 2010;31(5):411–5.

    Article  CAS  PubMed  Google Scholar 

  9. Anastasi E, Marchei GG, Viggiani V, Gennarini G, Frati L, Reale MG. HE4: a new potential early biomarker for the recurrence of ovarian cancer. Tumour Biol. 2010;31:113–9.

    Article  CAS  PubMed  Google Scholar 

  10. Hellstrom I, Heagerty PJ, Swisher EM, Liu P, Jaffar J, Agnew K, et al. Detection of the HE4 protein in urine as a biomarker for ovarian neoplasms. Cancer Lett. 2010;296:43–8.

    Article  CAS  PubMed  Google Scholar 

  11. Bingle L, Cross SS, High AS, Wallace WA, Rassl D, Yuan G, et al. WFDC2 (HE4): a potential role in the innate immunity of the oral cavity and respiratory tract and the development of adenocarcinomas of the lung. Respir Res. 2006;7:61–70.

    Article  PubMed  Google Scholar 

  12. Galgano MT, Hampton GM, Frierson Jr HF. Comprehensive analysis of HE4 expression in normal and malignant human tissues. Mod Pathol. 2006;19:847–53.

    CAS  PubMed  Google Scholar 

  13. Drapkin R, von Horsten HH, Lin Y, Mok SC, Crum CP, Welch WR, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res. 2005;65:2162–9.

    Article  CAS  PubMed  Google Scholar 

  14. Scholler N, Crawford M, Sato A, Drescher CW, O’Briant KC, Kiviat N, et al. Bead-based ELISA for validation of ovarian cancer early detection markers. Clin Cancer Res. 2006;12:2117–24.

    Article  CAS  PubMed  Google Scholar 

  15. Garber ME, Troyanskaya OG, Schluens K, Petersen S, Thaesler Z, Pacyna-Gengelbach M, et al. Diversity of gene expression in adenocarcinoma of the lung. Proc Natl Acad Sci USA. 2001;98:13784–9.

    Article  CAS  PubMed  Google Scholar 

  16. Endoh H, Tomida S, Yatabe Y, Konishi H, Osada H, Tajima K, et al. Prognostic model of pulmonary adenocarcinoma by expression profiling of eight genes as determined by quantitative real-time reverse transcriptase polymerase chain reaction. J Clin Oncol. 2004;22:811–9.

    Article  CAS  PubMed  Google Scholar 

  17. Bouchard D, Morisset D, Bourbonnais Y, Tremblay GM. Proteins with whey-acidic-protein motifs and cancer. Lancet Oncol. 2006;7:167–74.

    Article  CAS  PubMed  Google Scholar 

  18. Devoogdt N, Hassanzadeh Ghassabeh G, Zhang J, Brys L, De Baetselier P, Revets H. Secretory leukocyte protease inhibitor promotes the tumorigenic and metastatic potential of cancer cells. Proc Natl Acad Sci U S Am. 2003;100:5778–82.

    Article  CAS  Google Scholar 

  19. Ryu B, Jones J, Blades NJ, Parmigiani G, Hollingsworth MA, Hruban RH, et al. Relationships and differentially expressed genes among pancreatic cancers examined by large-scale serial analysis of gene expression. Cancer Res. 2002;62:819–26.

    CAS  PubMed  Google Scholar 

  20. Zhu H, Lam DC, Han KC, Tin VP, Suen WS, Wang E, et al. High resolution analysis of genomic aberrations by metaphase and array comparative genomic hybridization identifies candidate tumour genes in lung cancer cell lines. Cancer Lett. 2007;245:303–14.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We appreciate the technical support of Ms. Yoko Miyanari from the Department of Surgery II, Oita University Faculty of Medicine.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shin-ichi Yamashita.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamashita, Si., Tokuishi, K., Hashimoto, T. et al. Prognostic significance of HE4 expression in pulmonary adenocarcinoma. Tumor Biol. 32, 265–271 (2011). https://doi.org/10.1007/s13277-010-0118-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-010-0118-5

Keywords

Navigation