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Tissue biomarker development in a multicentre trial context: a feasibility study on the PETACC3 stage II and III colon cancer adjuvant treatment trial

Bosman, Fred T.
Tejpar, Sabine
Fiocca, Roberto
Van Cutsem, Eric
Kennedy, Richard D.
Dietrich, Daniel
Published in Clinical cancer research. 2009, vol. 15, no. 17, p. 5528-33
Abstract PURPOSE: We evaluated the feasibility of biomarker development in the context of multicenter clinical trials. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded (FFPE) tissue samples were collected from a prospective adjuvant colon cancer trial (PETACC3). DNA was isolated from tumor as well as normal tissue and used for analysis of microsatellite instability, KRAS and BRAF genotyping, UGT1A1 genotyping, and loss of heterozygosity of 18 q loci. Immunohistochemistry was used to test expression of TERT, SMAD4, p53, and TYMS. Messenger RNA was retrieved and tested for use in expression profiling experiments. RESULTS: Of the 3,278 patients entered in the study, FFPE blocks were obtained from 1,564 patients coming from 368 different centers in 31 countries. In over 95% of the samples, genomic DNA tests yielded a reliable result. Of the immmunohistochemical tests, p53 and SMAD4 staining did best with reliable results in over 85% of the cases. TERT was the most problematic test with 46% of failures, mostly due to insufficient tissue processing quality. Good quality mRNA was obtained, usable in expression profiling experiments. CONCLUSIONS: Prospective clinical trials can be used as framework for biomarker development using routinely processed FFPE tissues. Our results support the notion that as a rule, translational studies based on FFPE should be included in prospective clinical trials.
Keywords Antineoplastic Combined Chemotherapy ProtocolsCamptothecin/administration & dosage/analogs & derivativesChemotherapy, AdjuvantColonic Neoplasms/drug therapy/mortalityDisease-Free SurvivalFluorouracil/administration & dosageGlucuronosyltransferase/genetics/metabolismHumansMicrosatellite InstabilityOligonucleotide Array Sequence AnalysisPolymorphism, Single Nucleotide/geneticsProspective StudiesProto-Oncogene Proteins/genetics/metabolismProto-Oncogene Proteins B-raf/genetics/metabolismSmad4 Protein/metabolismTelomerase/metabolismTumor Markers, Biological/genetics/metabolismTumor Suppressor Protein p53/metabolismRas Proteins/genetics/metabolism
PMID: 19690194
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Research group Groupe Roth Arnaud (oncologie) (285)
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BOSMAN, Fred T. et al. Tissue biomarker development in a multicentre trial context: a feasibility study on the PETACC3 stage II and III colon cancer adjuvant treatment trial. In: Clinical cancer research, 2009, vol. 15, n° 17, p. 5528-33. doi: 10.1158/1078-0432.CCR-09-0741 https://archive-ouverte.unige.ch/unige:5493

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Deposited on : 2010-03-19

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