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 language | English |
|---|---|
| Pages (from-to) | 5528-5533 |
| Number of pages | 6 |
| Journal | Clinical Cancer Research |
| Volume | 15 |
| Issue number | 17 |
| DOIs | |
| Publication status | Published - Sep 1 2009 |
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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 journal › Article
}
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.
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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 -