Clinical and Translational Oncology

, Volume 12, Issue 6, pp 443–449 | Cite as

Expression of EGFR, HER-2/neu and KIT in germ cell tumours

  • Ignacio Durán
  • Adelaida García-Velasco
  • Claudio Ballestín
  • Elena García
  • Francisco Martínez-Tello
  • Gregory R. Pond
  • Rocío García-Carbonero
  • Hernán Cortés-Funés
  • Luis Paz-Ares
Research Articles



Germ cell tumours (GCTs) represent an extraordinarily chemosensitive malignancy. However, 20–30% of patients with advanced disease cannot be cured by currently available treatments. The role of tyrosine kinase receptors has been widely studied in other malignancies. Yet, limited information is available on GCTs.


One hundred and nine paraffin-embedded GCTs in 84 patients were assessed by immunohistochemistry for epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER-2)/neu and KIT (CD117) expression. Univariate and multivariate analyses were performed to evaluate their role as predictive and/or prognostic factors.


EGFR and HER-2/neu staining was detected in 28% and 13% of tumours, respectively, predominantly in nonseminomatous GCTs. KIT protein was almost universally expressed in seminomas (97%), being virtually absent in choriocarcinoma and teratocarcinoma subtypes. EGFR expression showed inverse association with tumour response of borderline significance. With a median follow-up of 10.6 years, no significant association was observed between the expression of any of these markers and relapsefree or overall survival.


EGFR, HER-2/neu and KIT have differential patterns of expression in GCTs according to histological subtypes. The expression of these markers in our series had no prognostic or predictive significance.


EGFR KIT HER-2/neu Germ cell tumours 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    De Vita VJ Jr, Hellman S, Rosenberg SA (eds) (2001) Cancer: principles and practice of oncology, 6th edn. Philadelphia, Lippincott-RavenGoogle Scholar
  2. 2.
    Bosl GJ, Motzer RJ (1997) Testicular germ-cell cancer. N Engl J Med 337:242–253CrossRefPubMedGoogle Scholar
  3. 3.
    Kondagunta GV, Sheinfeld J, Motzer RJ (2003) Recommendations of follow-up after treatment of germ cell tumors. Semin Oncol 30:382–389CrossRefPubMedGoogle Scholar
  4. 4.
    Arteaga CL (2002) Overview of epidermal growth factor receptor biology and its role as a therapeutic target in human neoplasia. Semin Oncol 29:3–9PubMedGoogle Scholar
  5. 5.
    Natali PG, Nicotra MR, Sures I et al (1992) Expression of c-KIT receptor in normal and transformed human nonlymphoid tissues. Cancer Res 52(22):6139–6143PubMedGoogle Scholar
  6. 6.
    Kemmer K, Corless CL, Fletcher JA et al (2004) KIT mutations are common in testicular seminomas. Am J Pathol 164(1):305–313PubMedGoogle Scholar
  7. 7.
    Tian Q, Frierson HF Jr, Krystal GW et al (1999) Activating c-KIT gene mutations in human germ cell tumors. Am J Pathol 154:1643–1647PubMedGoogle Scholar
  8. 8.
    International Germ Cell Cancer Collaborative Group (1997) International germ cell consensus classification: a prognostic-factor-based staging system for metastatic germ cell cancers. J Clin Oncol 15:594–603Google Scholar
  9. 9.
    World Health Organization (1979) WHO handbook for reporting results of cancer treatment. World Health Organization Offset Publication No. 48. Geneva, World Health OrganizationGoogle Scholar
  10. 10.
    World Health Organization (2004) World Health Organization (WHO) classification of tumors, 7th ed. Geneva, World Health OrganizationGoogle Scholar
  11. 11.
    Madani A, Kemmer K, Sweeney C et al (2003) Expression of KIT and epidermal growth factor receptor in chemotherapy refractory non-seminomatous germ-cell tumors. Ann Oncol 14:873–880CrossRefPubMedGoogle Scholar
  12. 12.
    Moroni M, Veronese S, Schiavo R et al (2001) Epidermal growth factor receptor expression and activation in nonseminomatous germ cell tumors. Clin Cancer Res 7:2770–2775PubMedGoogle Scholar
  13. 13.
    Kollmannsberger C, Mayer F, Pressler H et al (2002) Absence of c-KIT and members of the epidermal growth factor receptor family in refractory germ cell cancer. Cancer 95:301–308CrossRefPubMedGoogle Scholar
  14. 14.
    Hechelhammer L, Storkel S, Odermatt B et al (2003) Epidermal growth factor receptor is a marker for syncytiotrophoblastic cells in testicular germ cell tumors. Virchows Arch 443:28–31CrossRefPubMedGoogle Scholar
  15. 15.
    Soule S, Baldridge L, Kirkpatrick K et al (2002) HER-2/neu expression in germ cell tumours. J Clin Pathol 55(9):656–658CrossRefPubMedGoogle Scholar
  16. 16.
    Mandoky L, Geczi L, Bodrogi I et al (2003) Expression of HER-2/neu in testicular tumors. Anticancer Res 23(4):3447–3451PubMedGoogle Scholar
  17. 17.
    Izquierdo MA, Van der Valk P, Van Ark-Otte J et al (1995) Differential expression of the c-KIT proto-oncogene in germ cell tumours. J Pathol 177:253–258CrossRefPubMedGoogle Scholar
  18. 18.
    Strohmeyer T, Reese D, Press M et al (1995) Expression of the c-KIT proto-oncogene and its ligand stem cell factor (SCF) in normal and malignant human testicular tissue. J Urol 153:511–515CrossRefPubMedGoogle Scholar
  19. 19.
    Bokemeyer C, Kuczyk MA, Dunn T et al (1996) Expression of stem-cell factor and its receptor c-kit protein in normal testicular tissue and malignant germ-cell tumours. J Cancer Res Clin Oncol 122:301–306CrossRefPubMedGoogle Scholar
  20. 20.
    Einhorn LH, Brames MJ, Heinrich MC et al (2006) Phase II study of imatinib mesylate in chemotherapy refractory germ cell tumors expressing KIT. Am J Clin Oncol 29:12–13CrossRefPubMedGoogle Scholar
  21. 21.
    Piulats JM, Garcia del Muro X, Huddart R et al (2007) Phase II multicenter study of imatinib in patients with refractory germ cell tumors that express c-KIT. Proc Amer Assoc Cancer Res. Abstract 2648Google Scholar

Copyright information

© Feseo 2010

Authors and Affiliations

  • Ignacio Durán
    • 1
    • 5
  • Adelaida García-Velasco
    • 1
  • Claudio Ballestín
    • 2
  • Elena García
    • 2
  • Francisco Martínez-Tello
    • 2
  • Gregory R. Pond
    • 3
  • Rocío García-Carbonero
    • 4
  • Hernán Cortés-Funés
    • 1
  • Luis Paz-Ares
    • 1
  1. 1.Medical Oncology DepartmentHospital Universitario Doce de OctubreMadridSpain
  2. 2.Pathology DepartmentHospital Universitario Doce de OctubreMadridSpain
  3. 3.Biostatistics Department Princess Margaret HospitalUniversity Health NetworkTorontoCanada
  4. 4.Medical Oncology DepartmentHospital Severo Ochoa LeganésMadridSpain
  5. 5.Centro Integral Oncológico Clara CampalMadridSpain

Personalised recommendations