Tumour-Associated Transcripts and EGFR Deletion Variants in Colorectal Cancer in Primary Tumour, Metastases and Circulating Tumour Cells

Silke Lankiewicz,Silke Zimmermann,Eva Rother,Tim F Greten,Firouzeh Korangy,Christiane Hollmann

doi:10.1155/2008/460457

Silke Lankiewicz, Silke Zimmermann + Show 4 more

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https://doi.org/10.1155/2008/460457

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Abstract

The clinical relevance of circulating tumour cells (CTC) in peripheral blood of patients with colorectal cancer (CRC) has been described as an independent prognostic factor useful to monitor drug effects and clinical status. The aim of the present study was to compare the epidermal growth factor receptor (EGFR) status of primary tumour, related metastases and CTC of patients with CRC. Therefore, in addition to EGFR, the tumour-associated transcripts gastrointestinal tumour-associated antigen 733-2 (GA733-2) and carcinoembryonic antigen (CEA) were analyzed in a multiplex RT-PCR to characterize CTC. 55% patients were positive for CTC. EGFR expression was detected in 18% of these patients. EGFR was expressed more frequently in metastatic and primary tumour tissues as revealed by immunohistochemistry. Besides, detailed expression profiling of EGFR variants in various colorectal and glioma cell lines has been performed to generate positive controls, resulting in the discovery of two new transcript deletion variations (cEX12_15del, cEX12_14del) located on the extracellular domain of the EGFR.

Highlights

The biological properties of metastases may be quite different from those of the primary tumour as reviewed in [3]
Blood samples of 20 colorectal cancer (CRC) patients with liver metastases were analyzed for circulating tumour cells (CTC) using reverse transcriptase polymerase chain reaction (RT-PCR) and subsequent DNA fragment analysis
Since wild-type epidermal growth factor receptor (EGFR) seems to be rare on CTC in blood of metastatic CRC patients, the patients’ cDNA was examined for N-terminal EGFR variants

Summary

Introduction

The biological properties of metastases may be quite different from those of the primary tumour as reviewed in [3]. Recent efforts to determine CTC have used reverse transcriptase polymerase chain reaction (RT-PCR) to identify tumour-associated transcripts like GA733-2, CEA, cytokeratin 20 (CK-20) or EGFR combined with different separation methods like immunomagnetic enrichment, density gradient centrifugation or lyses of erythrocytes [14,29,30]. With these methods the comparison of the gene expression of the primary tumour, CTC and metastases can be undertaken to show similarities and to describe differences

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