Prospective evaluation of predictive and prognostic molecular markers in colorectal carcinomas
date: 15-17 September 2010
topic: Colorectal Cancer
organizer: European Society of Surgical Oncology
location: Bordeaux
Background: Treatment decisions for adjuvant therapy are usually performed after surgery respecting the TNM-criteria in colorectal carcinomas (CRC).
Molecular markers in the primary tumor may determine therapy response and prognosis and may be helpful for individualized treatment algorithms. But only few molecular markers are used during clinical routine until now.
New marker combinations must be evaluated for their clinical relevance. Material and methods: Gene expression profiling (HG-U133A, Affymetrix) of 80 CRC stage UICC I-III (UICC I, II, n=40; UICC III, n=40) was performed.
Data were analysed with emphasis on predictive markers for metastasis and angiogenesis. Differentially expressed genes between stage UICC I, II vs. III were validated by RT-PCR and immunohistochemistry.
Then a predictive and prognostic marker combination for a prospective evaluation was generated.
Results: Two predictive gene clusters for metastasis (e.g. ADAM22, LDN 16, WNT 16) and reduced angiogenesis (e.g. CXCL 11, CXCL9, CXCL 10) were identified which were associated with significantly reduced or prolonged survival of the patients. This set of genes will be evaluated prospectively with a new automated method, which enables the synchronous analyses of 100 transcripts in RNA from 4-5 slices of routinely paraffin embedded tissue (Polyprobe-Study, Erlangen, Frankfurt, Cologne, Germany) Conclusion: Prognostic and predictive marker signatures were identified in CRC by gene expression profiling. New technologies for the analysis of gene expression in routinely embedded paraffin tissues which can be easily implemented into the clinical routine will help to improve clinical decisions in near future.