Tyrosine kinase receptor expression in thymomas

  • John D. Henley
  • Oscar W. Cummings
  • Patrick J. Loehrer, Sr.
Original Paper



Promising new therapies for neoplasia include tyrosine kinase receptor antagonists. Tyrosine kinase oncogenes present an appealing anti-tumor drug target since they play an integral role in a variety of cellular responses including cell proliferation and differentiation. We previously demonstrated a high rate of epidermal growth factor receptor (EGFR) expression in advanced-stage thymic epithelial tumors. More recently, we have examined c-KIT (CD117) expression in a similar series of tumors.


Tumor from 35 patients seen at our institution for treatment of advanced-stage thymoma was available. Twenty thymomas and 15 thymic carcinomas were assessed for c-KIT expression. Tissue sections of tumor were stained immunohistochemically with anti-c-KIT (Oncogene). Either cytoplasmic or membrane staining was considered positive. Appropriate controls were performed. Positive staining for c-KIT was present in 12 tumors (11 thymic carcinomas and 1 thymoma).


In distinction to EGFR, c-KIT is expressed more commonly in thymic carcinomas (73% of carcinomas) than in thymoma (5% of thymomas).


An EGFR negative/c-KIT positive staining pattern is typical of thymic carcinoma, whereas thymomas are generally EGFR positive/c-KIT negative. Possible therapeutic implications of these observations remain to be determined.


c-KIT CD 117 Tyrosine kinase Thymoma Thymic carcinoma 



We thank Ms. C. Dodson and Mrs. L. Baldridge for their technical expertise and assistance with immunohistochemical staining.


  1. Bonner JA, Ezekiel MP, Robert F et al. (2000) Continued response following treatment with IMC-C225, an EGFr MoAb, combined with RT in advanced head and neck malignancies [abstr]. ASCO Program/Proceedings 19:5F. Available from URL: http://www.asco.org/prof/me/html/00abstracts/p/m_5F.htm (accessed 8 November 2000)Google Scholar
  2. Fontanini G, Vignati S, Bigini D et al. (1995) Epidermal growth factor receptor (EGFr) expression in non-small cell lung carcinomas correlates with metastatic involvement of hilar and mediastinal lymph nodes in the squamous subtype. Eur J Cancer 31A:178–183PubMedGoogle Scholar
  3. Gibson PC, Cooper K (2002) CD117 (KIT): a diverse protein with selective applications in surgical pathology. Adv Anat Pathol 9:65–69Google Scholar
  4. Gilhus NE, Jones M, Turley H et al. (1995) Oncogene proteins and proliferation antigens in thymomas: increased expression of epidermal growth factor receptor and Ki67 antigen. J Clin Pathol 48:447–455PubMedGoogle Scholar
  5. Gill GN, Bertics PJ, Santon JB (1987) Epidermal growth factor and its receptor. Mol Cell Endocrinol 51:169–186PubMedGoogle Scholar
  6. Hayashi Y, Ishii N, Obayashi C et al. (1995) Thymoma: tumour type related to expression of epidermal growth factor (EGF), EGF-receptor, p53, v-erb B and ras p21. Virchows Arch 426:43–50PubMedGoogle Scholar
  7. Henley JD, Koukoulis GK, Loehrer PJ Sr (2002) Epidermal growth factor receptor expression in invasive thymoma. J Cancer Res Clin Oncol 128:167–170Google Scholar
  8. Hoffmann T, Hafner D, Ballo H et al. (1997) Antitumor activity of anti-epidermal growth factor receptor monoclonal antibodies and cisplatin in ten human head and neck squamous cell carcinoma lines. Anticancer Res 17:4419–4425PubMedGoogle Scholar
  9. Issing WJ, Liebich C, Wustrow TP et al. (1996) Coexpression of epidermal growth factor receptor and TGF-alpha and survival in upper aerodigestive tract cancer. Anticancer Res 16:283–288PubMedGoogle Scholar
  10. Issing WJ, Wustrow TP, Heppt WJ (1993) Oncogenes related to head and neck cancer. Anticancer Res 13:2541–2551PubMedGoogle Scholar
  11. Kelloff GJ, Fay JR, Steele VE et al. (1996) Epidermal growth factor receptor tyrosine kinase inhibitors as potential cancer chemopreventives. Cancer Epidemiol Biomarkers Prev 5:657–666PubMedGoogle Scholar
  12. Levine GD, Rosai J (1978) Thymic hyperplasia and neoplasia: a review of current concepts. Human Pathol 9:495–515Google Scholar
  13. Longley BJ, Reguera MJ, Ma Y (2001) Classes of c-KIT activating mutations: proposed mechanisms of action and implications for disease classification and therapy. Leuk Res 25:571–576CrossRefPubMedGoogle Scholar
  14. Marino M, Muller-Hermelink HK (1985) Thymoma and thymic carcinoma. Relation of thymoma epithelial cells to the cortical and medullary differentiation of thymus. Virchows Arch [A] 407:119Google Scholar
  15. Pescarmona E, Pisacane A, Pignatelli E et al. (1993) Expression of epidermal and nerve growth factor receptors in human thymus and thymomas. Histopathology. 23:39–44Google Scholar
  16. Rubin MS, Shin DM, Pasmantier M et al. (2000) Monoclonal antibody (MoAb) IMC-C225, an anti-epidermal growth factor receptor (EGFr), for patients (Pts) with EGFr-positive tumors refractory to or in relapse from previous therapeutic regimens [abstr]. ASCO Program/Proceedings 19:1860. Available from URL: http://www.asco.org/prof/me/html/00abstracts/ibt/m_1860.htm (accessed 8 November 2000)Google Scholar
  17. Stanton P, Richards S, Reeves J et al. (1994) Epidermal growth factor receptor expression by human squamous cell carcinomas of the head and neck, cell lines and xenografts. Br J Cancer 70:427–433PubMedGoogle Scholar
  18. Takes RP, Baatenburg de Jong RJ, Schuuring E et al. (1998) Differences in expression of oncogenes and tumor suppressor genes in different sites of head and neck squamous cell. Anticancer Res 18:4793–4800PubMedGoogle Scholar
  19. Veale D, Ashcroft T, Marsh C et al. (1987) Epidermal growth factor receptors in non-small cell lung cancer. Br J Cancer. 55:513–516Google Scholar
  20. Woodburn JR (1999) The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol Ther 82:241–250PubMedGoogle Scholar
  21. Yang XD, Jia XC, Corvalan JRF et al. (2000) Therapeutic potential of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer treatment. ASCO Program/Proceedings 19:183. Available from URL: http://www.asco.org/prof/me/html/00abstracts/bmt/m_183.htm (accessed 8 November 2000)Google Scholar
  22. Yang XD, Jia XC, Corvalan JRF et al. (1999) Potent anti-tumor activity of ABX-EGF, a fully human monoclonal antibody to the epidermal growth factor receptor. ASCO Program/Proceedings 18:1766. Available from URL: http://www.asco.org/prof/me/html/00abstracts/bmt/m_183.htm (accessed 8 November 2000)Google Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • John D. Henley
    • 1
  • Oscar W. Cummings
    • 1
  • Patrick J. Loehrer, Sr.
    • 2
  1. 1.Department of PathologyIndiana University School of Medicine, Clarian Health PartnersIndianapolisUSA
  2. 2.Department of MedicineIndiana University School of MedicineIndianapolisUSA

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