Tumor Biology

, Volume 35, Issue 1, pp 33–38 | Cite as

Prognostic value of HER-2/neu expression in epithelial ovarian cancer: a meta-analysis

  • Yan Wang
  • Dong Wang
  • Mulan RenEmail author
Research Article


Various studies examined the relationship between human epidermal growth factor receptor 2 (HER-2/neu) overexpression and the clinical outcome in patients with ovarian cancer, but yielded conflicting results. Electronic databases updated in May 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between HER-2/neu overexpression and survival of patients with ovarian cancer. Survival data were aggregated and quantitatively analyzed. We conducted a final analysis of 3,055 patients from 20 eligible studies and evaluated the correlation between HER-2/neu overexpression and survival in patients with ovarian cancer. Combined hazard ratios suggested that HER-2/neu overexpression was not associated with a significant impact on survival, with the hazard ratio (HR) and 95 % confidence interval (CI) being 1.05 and 0.92–1.19, respectively, overall. When grouped according to the study design type, a statistically significant combined HR was found in retrospective studies (HR = 1.44, 95 % CI 1.14–1.75) and no statistically significant combined HR was found (HR = 0.96, 95 % CI 0.81–1.11) for prospective studies. HER-2/neu overexpression seems to have no significant impact on survival of ovarian cancer patients. However, a statistically significant combined HR was found in retrospective studies, but not in prospective studies.


HER-2/neu Ovarian cancer Prognosis Overall survival Meta-analysis 


Conflicts of interest



  1. 1.
    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60(5):277–300.PubMedCrossRefGoogle Scholar
  2. 2.
    Cannistra SA. Cancer of the ovary. N Engl J Med. 2004;351:2519–29.PubMedCrossRefGoogle Scholar
  3. 3.
    Winter III WE, Maxwell GL, Tian C, Carlson JW, Ozols RF, Rose PG, et al. Prognostic factors for III stage epithelial ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007;25:3621–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Oldenhuis CN, Oosting SF, Gietema JA, De Vries EG. Prognostic vs predictive value of biomarkers in oncology. Eur J Cancer. 2008;44:946–53.PubMedCrossRefGoogle Scholar
  5. 5.
    Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008;19:1523–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Altman DG. Systematic reviews of evaluations of prognostic variables. BMJ. 2001;323(7306):224–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Zhan P, Qian Q, Yu LK. Prognostic value of COX-2 expression in patients with non-small cell lung cancer: a systematic review and meta-analysis. J Thorac Dis. 2013;5(1):40–7. doi: 10.3978/j.issn.2072-1439.2013.01.02.PubMedCentralPubMedGoogle Scholar
  8. 8.
    Zhan P, Qian Q, Wan B, Yan TD, Yu LK. Prognostic value of TTF-1 expression in patients with non-small cell lung cancer: a meta-analysis. Transl Cancer Res. 2013. doi: 10.3978/j.issn.2218-676X.2013.02.08.Google Scholar
  9. 9.
    Zhan P, Wang Q, Qian Q, Yu LK. Megestrol acetate in cancer patients with anorexia-cachexia syndrome: a meta-analysis. Transl Cancer Res. 2013;2(2):74–9. doi: 10.3978/j.issn.2218-676X.2013.04.13.Google Scholar
  10. 10.
    Zhan P, Wang Q, Qian Q, Yu LK. Risk of venous thromboembolism with the erythropoiesis-stimulating agents (ESAs) for the treatment of cancer-associated anemia: a meta-analysis of randomized control trials. Chin Clin Oncol. 2013. doi: 10.3978/j.issn.2304-3865.2013.01.02.Google Scholar
  11. 11.
    Zhan P, Qian Q, Yu LK. Prognostic significance of Vascular endothelial growth factor expression in hepatocellular carcinoma tissue: a meta-analysis. Hepatobiliary Surg Nutr. 2013. doi: 10.3978/j.issn.2304-3881.2013.06.06.Google Scholar
  12. 12.
    Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17:2815–34.PubMedCrossRefGoogle Scholar
  13. 13.
    Yusuf S, Peto R, Lewis J, et al. Blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis. 1985;27:335–71.PubMedCrossRefGoogle Scholar
  14. 14.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.PubMedCrossRefGoogle Scholar
  15. 15.
    Egger M, Smith GD, Schneider M. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.PubMedCrossRefGoogle Scholar
  16. 16.
    Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.PubMedCrossRefGoogle Scholar
  17. 17.
    Berchuck A, Kamel A, Whitaker R, Kerns B, Olt G, Kinney R, et al. Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res. 1990;50:4087–91.PubMedGoogle Scholar
  18. 18.
    Fajac A, Benard J, Lhomme C, Rey A, Duvillard P, Rochard F, et al. c-erbB2 gene amplification and protein expression in ovarian epithelial tumors: evaluation of their respective prognostic significance by multivariate analysis. Int J Cancer. 1995;64:146–51.PubMedCrossRefGoogle Scholar
  19. 19.
    Kaufmann M, Von Minckwitz G, Kuhn W, Schmid H, Costa S, Goerttler K, et al. Combination of new biologic parameters as a prognostic index in epithelial ovarian carcinoma. Int J Gynecol Cancer. 1995;5:49–55.PubMedCrossRefGoogle Scholar
  20. 20.
    Medl M, Sevelda P, Czerwenka K, Dobianer K, Hanak H, Hruza C, et al. DNA amplification of HER-2/neu and INT-2 oncogenes in epithelial ovarian cancer. Gynecol Oncol. 1995;59:321–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Wang ZR, Liu W, Smith ST, Parrish RS, Young SR. c-myc and chromosome 8 centromere studies of ovarian cancer by interphase FISH. Exp Mol Pathol. 1999;66:140–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Davidson B, Gotlieb WH, Ben Baruch G, Nesland JM, Bryne M, Goldberg I, et al. E-cadherin complex protein expression and survival in ovarian carcinoma. Gynecol Oncol. 2000;79:362–71.PubMedCrossRefGoogle Scholar
  23. 23.
    Skirnisdottir I, Sorbe B, Seidal T. The growth factor receptors HER-2/neu and EGFR, their relationship, and their effects on the prognosis in early stage (FIGO I-II) epithelial ovarian carcinoma. Int J Gynecol Cancer. 2001;11:119–29.PubMedCrossRefGoogle Scholar
  24. 24.
    Camilleri-Broet S, Hardy-Bessard AC, Le Tourneau A, Paraiso D, Levrel O, Leduc B, et al. HER-2 overexpression is an independent marker of poor prognosis of advanced primary ovarian carcinoma: a multicenter study of the GINECO group. Ann Oncol. 2004;15:104–12.PubMedCrossRefGoogle Scholar
  25. 25.
    Nielsen JS, Jakobsen E, Holund B, Bertelsen K, Jakobsen A. Prognostic significance of p53, Her-2, and EGFR overexpression in borderline and epithelial ovarian cancer. Int J Gynecol Cancer. 2004;14:1086–96.PubMedCrossRefGoogle Scholar
  26. 26.
    Verri E, Guglielmini P, Puntoni M, Perdelli L, Papadia A, Lorenzi P, et al. HER2/neu oncoprotein overexpression in epithelial ovarian cancer: evaluation of its prevalence and prognostic significance. Clinical study Oncology. 2005;68:154–61.Google Scholar
  27. 27.
    Wang Y, Kristensen GB, Helland A, Nesland JM, Borresen-Dale AL, Holm R. Protein expression and prognostic value of genes in the erb-b signaling pathway in advanced ovarian carcinomas. Am J Clin Pathol. 2005;124:392–401.PubMedCrossRefGoogle Scholar
  28. 28.
    Castellvi J, Garcia A, Rojo F, Ruiz-Marcellan C, Gil A, Baselga J, et al. Phosphorylated 4E binding protein 1: a hallmark of cell signaling that correlates with survival in ovarian cancer. Cancer. 2006;107:1801–11.PubMedCrossRefGoogle Scholar
  29. 29.
    Surowiak P, Materna V, Kaplenko I, Spaczynski M, Dietel M, Lage H, et al. Topoisomerase 1A, HER/2neu and Ki67 expression in paired primary and relapse ovarian cancer tissue samples. Histol Histopathol. 2006;21:713–20.PubMedGoogle Scholar
  30. 30.
    Malamou-Mitsi V, Crikoni O, Timotheadou E, Aravantinos G, Vrettou E, Agnantis N, et al. Prognostic significance of HER-2, p53 and Bcl-2 in patients with epithelial ovarian cancer. Anticancer Res. 2007;27:1157–65.PubMedGoogle Scholar
  31. 31.
    Pils D, Pinter A, Reibenwein J, Alfanz A, Horak P, Schmid BC, et al. In ovarian cancer the prognostic influence of HER2/neu is not dependent on the CXCR4/SDF-1 signalling pathway. Br J Cancer. 2007;96:485–91.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Steffensen KD, Waldstrom M, Jeppesen U, Jakobsen E, Brandslund I, Jakobsen A. The prognostic importance of cyclooxygenase 2 and HER2 expression in epithelial ovarian cancer. International Journal of Gynecological Cancer. 2007;17:798–807.PubMedCrossRefGoogle Scholar
  33. 33.
    Tuefferd M, Couturier J, Penault-Llorca F, Vincent-Salomon A, Broet P, Guastalla JP, et al. HER2 status in ovarian carcinomas: a multicenter GINECO study of 320 patients. PLoS One. 2007;2(11):e1138.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    de Graeff P, Crijns AP, Ten Hoor KA, Klip HG, Hollema H, Oien K, et al. The ErbB signalling pathway: protein expression and prognostic value in epithelial ovarian cancer. Br J Cancer. 2008;99:341–9.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Garcia-Velasco A, Mendiola C, Sanchez-Munoz A, Ballestin C, Colomer R, Cortes-Funes H. Prognostic value of hormonal receptors, p53, ki67 and HER2/neu expression in epithelial ovarian carcinoma. Clin Transl Oncol. 2008;10:367–71.PubMedCrossRefGoogle Scholar
  36. 36.
    Tomsova M, Melichar B, Sedlakova I, Steiner I. Prognostic significance of CD3+ tumor-infiltrating lymphocytes in ovarian carcinoma. Gynecol Oncol. 2008;108:415–20.PubMedCrossRefGoogle Scholar
  37. 37.
    Shih C, Padhy L, Murray M, Weinberg RA. Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature. 1981;260:261–4.CrossRefGoogle Scholar
  38. 38.
    Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244:707–12.PubMedCrossRefGoogle Scholar
  39. 39.
    Begg CB, Berlin JA. Publication bias: a problem in interpreting medical data. J R Stat Soc A. 1988;151:419–63.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  1. 1.Department of Obstetrics and Gynecology, Zhongda HospitalSoutheast UniversityNanjingChina
  2. 2.Southeast University Medical SchoolNanjingChina

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