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Expression of Mutated Epidermal Growth Factor Receptor by Non-Small Cell Lung Carcinomas¹

Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 [I. E. G., G. P. A., P. S., A. J. W., J. R. T., L. M. W.], and the Preuss Laboratory for Brain Tumor Research, Duke University Medical Center, Durham, North Carolina 27710 [D. D. B.]

The development of novel immunotherapy strategies for non-small cell lung cancer (NSCLC) will be facilitated by the identification of tumor-specific targets. Although the epidermal growth factor receptor (EGFR) is overexpressed in many cases of NSCLC, its wide distribution in normal tissue may limit its suitability as an immunotherapeutic target. However, mutations within the EGFR that are unique to malignancies may provide specific targets for immunotherapeutic intervention. For example, one mutant form, the type III deletion mutant of the EGFR, that has been identified in glioblastomas contains a novel peptide sequence in its extracellular domain which is detectable by anti-peptide antisera. In this study, the prevalence of this type of mutation of the EGFR in NSCLC was determined. Thirty-two frozen sections of primary NSCLC were examined by immunocytochemistry to determine the presence of native and mutated EGFR. Native EGFR was overexpressed in 12 of the 32 sections and a diffuse cellular distribution of the EGFR type III deletion mutation was identified in five (16%) of the specimens (2 of 13 squamous, 2 of 2 mixed, 0 of 10 adenocarcinoma, and 1 of 7 undifferentiated). This mutated EGFR was not detected in sections of normal breast, lung, skin, ovary, colon, kidney, endometrium, and placenta. The type III EGFR deletion mutant, expressed in some cases of NSCLC, may be a molecularly defined, tumor-specific antigen in lung cancer.

¹ Supported by National Cancer Institute Grants CA06927, CA50633, and CA51880 and the Bernard A. and Rebecca S. Bernard Foundation.

² Present address: Department of Pathology and Laboratory Medicine, Temple University, Philadelphia, PA 19144.

³ To whom requests for reprints should be addressed, at Fox Chase Cancer Center, Department of Medical Oncology, 7701 Burholme Avenue, Philadelphia, PA 19111.

Received 3/19/93. Accepted 6/ 3/93.

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