Tissue biomarker development in a multicentre trial context

A feasibility study on the PETACC3 stage II and III colon cancer adjuvant treatment trial

Fred T. Bosman, Pu Yan, Sabine Tejpar, Roberto Fiocca, Eric Van Cutsem, Richard D. Kennedy, Daniel Dietrich, Arnaud Roth

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5528-5533
Number of pages6
JournalClinical Cancer Research
Volume15
Issue number17
DOIs
Publication statusPublished - Sep 1 2009

Fingerprint

Feasibility Studies
Paraffin
Colonic Neoplasms
Formaldehyde
Multicenter Studies
Biomarkers
Clinical Trials
Microsatellite Instability
Messenger RNA
Loss of Heterozygosity
DNA
Therapeutics
Research Design
Immunohistochemistry
Staining and Labeling
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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.; Yan, Pu; Tejpar, Sabine; Fiocca, Roberto; Van Cutsem, Eric; Kennedy, Richard D.; Dietrich, Daniel; Roth, Arnaud.

In: Clinical Cancer Research, Vol. 15, No. 17, 01.09.2009, p. 5528-5533.

Research output: Contribution to journalArticle

Bosman, Fred T. ; Yan, Pu ; Tejpar, Sabine ; Fiocca, Roberto ; Van Cutsem, Eric ; Kennedy, Richard D. ; Dietrich, Daniel ; Roth, Arnaud. / 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, No. 17. pp. 5528-5533.
@article{694e827a77534a48a06ca2f9b0f19c7c,
title = "Tissue biomarker development in a multicentre trial context: A feasibility study on the PETACC3 stage II and III colon cancer adjuvant treatment trial",
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.",
author = "Bosman, {Fred T.} and Pu Yan and Sabine Tejpar and Roberto Fiocca and {Van Cutsem}, Eric and Kennedy, {Richard D.} and Daniel Dietrich and Arnaud Roth",
year = "2009",
month = "9",
day = "1",
doi = "10.1158/1078-0432.CCR-09-0741",
language = "English",
volume = "15",
pages = "5528--5533",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "17",

}

TY - JOUR

T1 - Tissue biomarker development in a multicentre trial context

T2 - A feasibility study on the PETACC3 stage II and III colon cancer adjuvant treatment trial

AU - Bosman, Fred T.

AU - Yan, Pu

AU - Tejpar, Sabine

AU - Fiocca, Roberto

AU - Van Cutsem, Eric

AU - Kennedy, Richard D.

AU - Dietrich, Daniel

AU - Roth, Arnaud

PY - 2009/9/1

Y1 - 2009/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=69949094407&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69949094407&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-09-0741

DO - 10.1158/1078-0432.CCR-09-0741

M3 - Article

VL - 15

SP - 5528

EP - 5533

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 17

ER -