Abstract

BackgroundProteins overexpressed on the surface of tumor cells can be selectively targeted. Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are among the most often targeted proteins. The level and stability of expression in both primary tumors and corresponding metastases is crucial in the assessment of a receptor as target for imaging in nuclear medicine and for various forms of therapy. So far, the expression of EGFR and HER2 has only been determined in primary cervical cancers, and we have not found published data regarding the receptor status in corresponding metastatic lesions. The goal of this study was to evaluate whether any of these receptors are suitable as target for clinical diagnosis and therapy.MethodsExpression of EGFR and HER2 was investigated immunohistochemically in both lymph node metastases and corresponding primary cervical cancers (n = 53). HER2 and EGFR expression was scored using HercepTest criteria (0, 1+, 2+ or 3+).ResultsEGFR overexpression (2+ or 3+) was found in 64% (35/53) of the primary cervical tumors and 60% (32/53) of the corresponding lymph node metastases. There was a good concordance between the primary tumors and the paired metastases regarding EGFR expression. Only four patients who had 2+ or 3+ in the primary tumors changed to 0 or 1+ in lymph node metastases, and another two cases changed the other way around. None of the primary tumors or the lymph node metastases expressed HER2 protein.ConclusionThe EGFR expression seems to be common and stable during cervical cancer metastasis, which is encouraging for testing of EGFR targeted radiotherapy. HER2 appears to be of poor interest as a potential target in the treatment of cervical cancer.

Highlights

  • Proteins overexpressed on the surface of tumor cells can be selectively targeted

  • We found that the frequency of Epidermal growth factor receptor (EGFR) overexpression in lymph node metastases was approximately as high as in the primary lesions of cervical cancer

  • If membrane staining in more than 10% of the tumor cells was defined as positive EGFR expression, regardless of pattern of cellular membrane staining, only 3 changes could be observed: two cases from positive to negative when the primary lesions were compared to the corresponding lymph node metastases, and one case changed the other way around

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Summary

Introduction

Proteins overexpressed on the surface of tumor cells can be selectively targeted. Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are among the most often targeted proteins. Concurrent cisplatin-based chemoradiotherapy has been considered as the standard therapeutic modality for locally advanced cervical cancer [3,4,5,6]. Such treatment remains suboptimal with histopathological residual tumor observed in 40–50% of patients [7,8]. The testing of molecular targeted therapies against cervical cancer is a logical step to follow [11] Another strategy is receptor-mediated tumor targeted radiotherapy [12], which is based on the delivery of therapeutically relevant radionuclides directly to disseminated tumor cells, with hopefully minimal damage to normal tissues

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