PMID- 17785566
OWN - NLM
STAT- MEDLINE
DCOM- 20070925
LR  - 20070905
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 13
IP  - 17
DP  - 2007 Sep 1
TI  - Significance of HER2 low-level copy gain in Barrett's cancer: implications for 
      fluorescence in situ hybridization testing in tissues.
PG  - 5115-23
AB  - PURPOSE: HER2 may be a relevant biomarker in Barrett's cancer. We compared three 
      HER2 laboratory methods, standard fluorescence in situ hybridization (FISH), 
      image-based three-dimensional FISH in thick (16 microm) sections, and 
      immunohistochemistry, to predict patient outcome. EXPERIMENTAL DESIGN: Tissue 
      microarray sections from 124 Barrett's cancer patients were analyzed by standard 
      FISH on thin (4 microm) sections and by image-based three-dimensional FISH on 
      thick (16 microm) sections for HER2 and chromosome-17, as well for p185(HER2) by 
      immunohistochemistry. Correlations with clinical and follow-up data were 
      examined. RESULTS: Only three-dimensional FISH on thick (16 microm) sections 
      revealed HER2 gene copy gain to be associated with increased disease-specific 
      mortality (relative risk, 2.1; 95% confidence interval, 1.06-4.26; P = 0.033). In 
      contrast, standard FISH on thin (4 microm) sections and immunohistochemistry 
      failed to predict clinical outcome. Low-level gain of HER2 occurred frequently in 
      Barrett's cancer (>or=2.5-4.0 HER2 copies, 59.7%; HER2-to-chromosome-17 ratio, 
      >or=1.1-2.0; 61.2%) and defined a subpopulation for patient outcome as 
      unfavorable as HER2 gene amplification [disease-free survival, P = 0.017 (HER2 
      copies)]. This low-level group was neither definable by standard FISH nor 
      immunohistochemistry. No prognostic significance was found for chromosome-17 
      aneusomy. CONCLUSIONS: Low-level copy gains of HER2 define a biologically 
      distinct subpopulation of Barrett's cancer patients. Importantly, these subtle 
      copy number changes are not reliably detected by standard FISH in thin (4 microm) 
      tissue sections, highlighting a thus far unrecognized weakness in HER2 FISH 
      testing. These results should be taken into account for accurate evaluation of 
      biomarkers by FISH and for HER2 FISH testing in tissue sections.
FAU - Rauser, Sandra
AU  - Rauser S
AD  - Institute of Pathology , GSF-National Research Center for Environment and Health, 
      Neuherberg, Germany.
FAU - Weis, Roland
AU  - Weis R
FAU - Braselmann, Herbert
AU  - Braselmann H
FAU - Feith, Marcus
AU  - Feith M
FAU - Stein, Hubert J
AU  - Stein HJ
FAU - Langer, Rupert
AU  - Langer R
FAU - Hutzler, Peter
AU  - Hutzler P
FAU - Hausmann, Michael
AU  - Hausmann M
FAU - Lassmann, Silke
AU  - Lassmann S
FAU - Siewert, Jorg Rudiger
AU  - Siewert JR
FAU - Hofler, Heinz
AU  - Hofler H
FAU - Werner, Martin
AU  - Werner M
FAU - Walch, Axel
AU  - Walch A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
SB  - IM
MH  - Aged
MH  - Barrett Esophagus/*complications
MH  - Chromosomes, Human, Pair 17
MH  - Esophageal Neoplasms/*genetics/pathology
MH  - *Gene Dosage
MH  - *Genes, erbB-2
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
EDAT- 2007/09/06 09:00
MHDA- 2007/09/26 09:00
CRDT- 2007/09/06 09:00
PHST- 2007/09/06 09:00 [pubmed]
PHST- 2007/09/26 09:00 [medline]
PHST- 2007/09/06 09:00 [entrez]
AID - 13/17/5115 [pii]
AID - 10.1158/1078-0432.CCR-07-0465 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2007 Sep 1;13(17):5115-23. doi: 10.1158/1078-0432.CCR-07-0465.