Molecular Diagnostics

British Journal of Cancer (2006) 95, 218–225. doi:10.1038/sj.bjc.6603206 www.bjcancer.com
Published online 6 June 2006

Biomarker selection for detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT–PCR

L Ohlsson1, M-L Hammarström1, A Israelsson1, L Näslund1, Å Öberg2, G Lindmark3 and S Hammarström1

  1. 1Department of Clinical Microbiology, Immunology, Umeå University, SE-90185 Umeå, Sweden
  2. 2Department of Surgery and Perioperative Sciences, Surgery, Umeå University, SE-90185 Umeå, Sweden
  3. 3Department of Surgery, Helsingborgs Lasarett, Lund University, SE-25187 Helsingborg, Sweden

Correspondence: Dr S Hammarström;, E-mail: Sten.Hammarstrom@climi.umu.se

Received 22 December 2005; Revised 27 April 2006; Accepted 11 May 2006; Published online 6 June 2006.

Top

Abstract

Accurate identification of lymph node involvement is critical for successful treatment of patients with colorectal carcinoma (CRC). Real-time quantitative RT–PCR with a specific probe and RNA copy standard for biomarker mRNA has proven very powerful for detection of disseminated tumour cells. Which properties of biomarker mRNAs are important for identification of disseminated CRC cells? Seven biomarker candidates, CEA, CEACAM1-S/L, CEACAM6, CEACAM7-1/2, MUC2, MMP7 and CK20, were compared in a test-set of lymph nodes from 51 CRC patients (Dukes' A–D) and 10 controls. Normal colon epithelial cells, primary tumours, and different immune cells were also analysed. The biomarkers were ranked according to: (1) detection of haematoxylin/eosin positive nodes, (2) detection of Dukes' A and B patients, who developed metastases during a 54 months follow-up period and (3) identification of patients with Dukes' C and D tumours using the highest value of control nodes as cutoff. The following properties appear to be of importance; (a) no expression in immune cells, (b) relatively high and constant expression in tumour tissue irrespective of Dukes' stage and (c) no or weak downregulation in tumours compared to normal tissue. CEA fulfilled these criteria best, followed by CK20 and MUC2.

Keywords:

carcinoembryonic antigen (CEA), CEA cell adhesion molecule (CEACAM), mucin 2 (MUC2), cytokeratin 20 (CK20), matrix metalloproteinase 7 (MMP7).

Top

MORE ARTICLES LIKE THIS