PMID- 26542057
OWN - NLM
STAT- MEDLINE
DCOM- 20161219
LR  - 20181202
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 22
IP  - 7
DP  - 2016 Apr 1
TI  - DNA Topoisomerase I Gene Copy Number and mRNA Expression Assessed as Predictive 
      Biomarkers for Adjuvant Irinotecan in Stage II/III Colon Cancer.
PG  - 1621-31
LID - 10.1158/1078-0432.CCR-15-0561 [doi]
AB  - PURPOSE: Prospective-retrospective assessment of the TOP1 gene copy number and 
      TOP1 mRNA expression as predictive biomarkers for adjuvant irinotecan in stage 
      II/III colon cancer. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded 
      tissue microarrays were obtained from an adjuvant colon cancer trial (PETACC3) 
      where patients were randomized to 5-fluorouracil/folinic acid with or without 
      additional irinotecan. TOP1 copy number status was analyzed by fluorescence in 
      situ hybridization (FISH) using a TOP1/CEN20 dual-probe combination. TOP1 mRNA 
      data were available from previous analyses. RESULTS: TOP1 FISH and follow-up data 
      were obtained from 534 patients. TOP1 gain was identified in 27% using a 
      single-probe enumeration strategy (>/=4 TOP1 signals per cell) and in 31% when 
      defined by a TOP1/CEN20 ratio >/= 1.5. The effect of additional irinotecan was not 
      dependent on TOP1 FISH status.TOP1 mRNA data were available from 580 patients 
      with stage III disease. Benefit of irinotecan was restricted to patients 
      characterized by TOP1 mRNA expression >/= third quartile (RFS: HRadjusted, 0.59;P= 
      0.09; OS: HRadjusted, 0.44;P= 0.03). The treatment by TOP1 mRNA interaction was 
      not statistically significant, but in exploratory multivariable fractional 
      polynomial interaction analysis, increasing TOP1 mRNA values appeared to be 
      associated with increasing benefit of irinotecan. CONCLUSIONS: In contrast to the 
      TOP1 copy number, a trend was demonstrated for a predictive property of TOP1 mRNA 
      expression. On the basis of TOP1 mRNA, it might be possible to identify a 
      subgroup of patients where an irinotecan doublet is a clinically relevant option 
      in the adjuvant setting of colon cancer.
CI  - (c)2015 American Association for Cancer Research.
FAU - Nygard, Sune Boris
AU  - Nygard SB
AD  - University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, 
      Denmark.
FAU - Vainer, Ben
AU  - Vainer B
AD  - Department of Pathology, Rigshospitalet, Copenhagen University Hospital, 
      Copenhagen, Denmark.
FAU - Nielsen, Signe Lykke
AU  - Nielsen SL
AD  - University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, 
      Denmark.
FAU - Bosman, Fred
AU  - Bosman F
AD  - University of Lausanne, University Institute of Pathology, Lausanne, Switzerland.
FAU - Tejpar, Sabine
AU  - Tejpar S
AD  - Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium.
FAU - Roth, Arnaud
AU  - Roth A
AD  - Oncosurgery Unit, University Hospital of Geneva, Geneva, Switzerland.
FAU - Delorenzi, Mauro
AU  - Delorenzi M
AD  - SIB Swiss Institute of Bioinformatics, Bioinformatics Core Facility, Lausanne, 
      Switzerland. University of Lausanne, Ludwig Center for Cancer Research, Lausanne, 
      Switzerland. Oncology Department, University of Lausanne, Lausanne, Switzerland.
FAU - Brunner, Nils
AU  - Brunner N
AD  - University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, 
      Denmark. nbr@sund.ku.dk.
FAU - Budinska, Eva
AU  - Budinska E
AD  - Masaryk University, Institute of Biostatistics and Analyses, Brno, Czech 
      Republic.
LA  - eng
PT  - Journal Article
DEP - 20151105
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Biomarkers)
RN  - 0 (RNA, Messenger)
RN  - 0 (Topoisomerase I Inhibitors)
RN  - 7673326042 (Irinotecan)
RN  - EC 5.99.1.2 (DNA Topoisomerases, Type I)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
MH  - Antineoplastic Agents, Phytogenic/therapeutic use
MH  - Biomarkers
MH  - Camptothecin/analogs & derivatives/therapeutic use
MH  - Chemotherapy, Adjuvant
MH  - Colonic Neoplasms/diagnosis/drug therapy/*genetics/*mortality
MH  - DNA Topoisomerases, Type I/*genetics
MH  - Female
MH  - *Gene Dosage
MH  - *Gene Expression
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Irinotecan
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Neoplasm Staging
MH  - Prognosis
MH  - RNA, Messenger/*genetics
MH  - Topoisomerase I Inhibitors/therapeutic use
EDAT- 2015/11/07 06:00
MHDA- 2016/12/20 06:00
CRDT- 2015/11/07 06:00
PHST- 2015/03/11 00:00 [received]
PHST- 2015/10/12 00:00 [accepted]
PHST- 2015/11/07 06:00 [entrez]
PHST- 2015/11/07 06:00 [pubmed]
PHST- 2016/12/20 06:00 [medline]
AID - 1078-0432.CCR-15-0561 [pii]
AID - 10.1158/1078-0432.CCR-15-0561 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2016 Apr 1;22(7):1621-31. doi: 10.1158/1078-0432.CCR-15-0561. 
      Epub 2015 Nov 5.