Analysis of ErbB receptors in pulmonary carcinoid tumors

Otis B. Rickman, Pawan K. Vohra, Bharati Sanyal, Julie A. Vrana, Marie Christine Aubry, Dennis A Wigle, Charles F. Thomas

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Abstract

Purpose: This study aimed to investigate the expression of the ErbB family of receptor tyrosine kinases in pulmonary typical carcinoid and atypical carcinoid tumors and to understand the role of epidermal growth factor receptor (EGFR) signaling in pulmonary carcinoid tumor proliferation. Experimental Design: Surgically resected typical carcinoid (n = 24) and atypical carcinoid (n = 7) tumor tissues were analyzed by immunohistochemical staining for EGFR, ErbB2, ErbB3, and ErbB4. Sequencing of tumor DNA of exons 18 to 21 of the EGFR gene and the KRAS gene was carried out. Biochemical analysis of lung carcinoid cell lines was used to investigate EGFR signal transduction and response to erlotinib inhibition. Results: The analysis showed that 45.8% of typical carcinoid and 28.6% of atypical carcinoid tumors express EGFR, 100% of the tumors lack expression of ErbB2, and 100% have moderate to intense staining for ErbB3 and ErbB4. Sequencing of tumor DNA of exons 18 to 21 of the EGFR gene revealed the absence of tyrosine kinase domain mutations in these tumors. Instead, 80.6% tumors harbored a synonymous single nucleotide polymorphism in exon 20. Because EGFR and KRAS mutations tend not to be present at the same time, we sequenced the KRAS gene from pulmonary carcinoid tumor DNA and found that 100% were wild-type. Using a lung carcinoid cell line that expresses EGFR, we found that erlotinib reduced proliferation by inhibiting EGFR signal transduction. Conclusions: Our findings suggest clinical potential for the use of EGFR inhibitors in the treatment of patients with pulmonary carcinoid tumors, particularly for patients with EGFR-positive pulmonary carcinoid tumors not amenable to surgical resection.

Original languageEnglish (US)
Pages (from-to)3315-3324
Number of pages10
JournalClinical Cancer Research
Volume15
Issue number10
DOIs
StatePublished - May 15 2009

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Carcinoid Tumor
Epidermal Growth Factor Receptor
Lung
erbB-1 Genes
Exons
Neoplasms
DNA Sequence Analysis
Protein-Tyrosine Kinases
ErbB Receptors
Signal Transduction
Staining and Labeling
Cell Line
Mutation
Genes
Single Nucleotide Polymorphism
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Rickman, O. B., Vohra, P. K., Sanyal, B., Vrana, J. A., Aubry, M. C., Wigle, D. A., & Thomas, C. F. (2009). Analysis of ErbB receptors in pulmonary carcinoid tumors. Clinical Cancer Research, 15(10), 3315-3324. https://doi.org/10.1158/1078-0432.CCR-08-2549

Analysis of ErbB receptors in pulmonary carcinoid tumors. / Rickman, Otis B.; Vohra, Pawan K.; Sanyal, Bharati; Vrana, Julie A.; Aubry, Marie Christine; Wigle, Dennis A; Thomas, Charles F.

In: Clinical Cancer Research, Vol. 15, No. 10, 15.05.2009, p. 3315-3324.

Research output: Contribution to journalArticle

Rickman, OB, Vohra, PK, Sanyal, B, Vrana, JA, Aubry, MC, Wigle, DA & Thomas, CF 2009, 'Analysis of ErbB receptors in pulmonary carcinoid tumors', Clinical Cancer Research, vol. 15, no. 10, pp. 3315-3324. https://doi.org/10.1158/1078-0432.CCR-08-2549
Rickman OB, Vohra PK, Sanyal B, Vrana JA, Aubry MC, Wigle DA et al. Analysis of ErbB receptors in pulmonary carcinoid tumors. Clinical Cancer Research. 2009 May 15;15(10):3315-3324. https://doi.org/10.1158/1078-0432.CCR-08-2549
Rickman, Otis B. ; Vohra, Pawan K. ; Sanyal, Bharati ; Vrana, Julie A. ; Aubry, Marie Christine ; Wigle, Dennis A ; Thomas, Charles F. / Analysis of ErbB receptors in pulmonary carcinoid tumors. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 10. pp. 3315-3324.
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