Abstract
The expression of human epidermal growth factor receptor (HER) family proteins was examined in specimens of 52 non-small cell lung cancers to evaluate their significance in tumor cell proliferation and their response to gefitinib. Epidermal growth factor receptor (EGFR; HER1) protein was expressed most frequently (43/52 cases). HER2 and HER3 were detected in 13 and 18 cases, respectively. HER4 was detected in only one case of squamous cell carcinoma. HER3 was expressed preferentially in adenocarcinomas of the papillary type. In most HER3-positive cases with or without other HER family proteins, the Ki-67 labelling index (18.2%) was significantly lower than in HER3-negative cases (30.6%) (P<0.05). Adenocarcinomas co-expressing EGFR, HER2 and HER3 frequently showed both a good response to gefitinib (6/7 cases) and a mutation of EGFR (4/6 cases). However, cases with a favourable response to gefitinib did not always express EGFR. Gefitinib appears to suppress growth signal pathways other than EGFR-tyrosine kinase activation in non-small cell lung cancers.
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