Comparison of the epidermal growth factor receptor protein expression between primary non-small cell lung cancer and paired lymph node metastases: implications for targeted nuclide radiotherapy

Chuangzhou Rao,Li Shen,Jianhua Ma,Qichun Wei,Jian Li,Qiongge Hu,Chen Zhang

doi:10.1186/1756-9966-29-7

Abstract

BackgroundThe knowledge of Epidermal growth factor receptor (EGFR) expression in metastases of NSCLC was limited. In receptor-mediated targeted nuclide radiotherapy, tumor cells are killed with delivered radiation and therapeutic efficiency is mainly dependent on the receptor expression. Thus, the level and stability of receptor expression in both primary tumors and corresponding metastases is crucial in the assessment of a receptor as target. The goal of this study was to evaluate whether EGFR is suitable as target for clinical therapy.MethodsExpression of EGFR was investigated immunohistochemically in paired samples of lymph node metastases and corresponding NSCLC primary lesions (n = 51). EGFR expression was scored as 0, 1+, 2+ or 3+.ResultsPositive (1+, 2+ or 3+) EGFR immunostaining was evident in 36 of 47 (76.6%) analysed NSCLC primary tumors, and in 78.7% of the corresponding lymph node metastases. When EGFR expression is classified as positive or negative, discordance between the primary tumors and the corresponding metastases was observed in 5 cases (10.6%). EGFR overexpression (2+ or 3+) was found in 53.2% (25/47) of the NSCLC primary tumors and 59.6% of the corresponding metastases. Nine out of the 47 paired samples (19.2%) were discordant: Only three patients who had EGFR overexpression in the primary tumors showed EGFR downregulation (0 or 1+) in lymph node metastases, while six patients changed the other way around.ConclusionsThe EGFR expression in the primary tumor and the corresponding metastasis is discordant in about 10% of the patients. When overexpression is considered, the discordance is observed in about 20% of the cases. However, concerning EGFR overexpression in the primary tumors, similar expression in the metastases could be predicted with a reasonably high probability, which is encouraging for testing of EGFR targeted nuclide radiotherapy.

Highlights

The knowledge of Epidermal growth factor receptor (EGFR) expression in metastases of Non-small cell lung cancer (NSCLC) was limited
Example of staining pattern for a primary tumor and the corresponding metastasis is shown in Fig. 1A and 1B
Comparison of the EGFR status between primary tumors and metastases When EGFR expression is classified as positive (1+, 2+ or 3+) or negative, a discordance was observed in 5 cases (10.6%): in 2 cases, EGFR was expressed in the primary tumor but not in the metastasis, while three samples showed EGFR expression in the metastasis but not in the primary tumor

Summary

Introduction

The knowledge of Epidermal growth factor receptor (EGFR) expression in metastases of NSCLC was limited. In receptor-mediated targeted nuclide radiotherapy, tumor cells are killed with delivered radiation and therapeutic efficiency is mainly dependent on the receptor expression. The level and stability of receptor expression in both primary tumors and corresponding metastases is crucial in the assessment of a receptor as target. Of all patients with newly diagnosed NSCLC, 65-75% have inhibitors (TKIs) against Epidermal growth factor receptor (EGFR), such as gefitinib and erlotinib, have been developed with the hope of improving response to traditional cytotoxic agents, only a limited percentage (12%27%) of patients seem to benefit from such agents [10,11,12,13].

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