PMID- 16166438
OWN - NLM
STAT- MEDLINE
DCOM- 20051108
LR  - 20220330
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 11
IP  - 18
DP  - 2005 Sep 15
TI  - Diagnostic evaluation of HER-2 as a molecular target: an assessment of accuracy 
      and reproducibility of laboratory testing in large, prospective, randomized 
      clinical trials.
PG  - 6598-607
AB  - PURPOSE: To critically assess the accuracy and reproducibility of human epidermal 
      growth factor receptor type 2 (HER-2) testing in outside/local community-based 
      hospitals versus two centralized reference laboratories and its effect on 
      selection of women for trastuzumab (Herceptin)-based clinical trials. 
      EXPERIMENTAL DESIGN: Breast cancer specimens from 2,600 women were prospectively 
      evaluated by fluorescence in situ hybridization (FISH) for entry into Breast 
      Cancer International Research Group (BCIRG) clinical trials for HER-2-directed 
      therapies. RESULTS: HER-2 gene amplification by FISH was observed in 657 of the 
      2,502 (26%) breast cancers successfully analyzed. Among 2,243 breast cancers with 
      central laboratory immunohistochemistry (10H8-IHC) analysis, 504 (22.54%) showed 
      overexpression (2+ or 3+). Outside/local laboratories assessed HER-2 status by 
      immunohistochemistry in 1,536 of these cases and by FISH in 131 cases. Overall, 
      the HER-2 alteration status determined by outside/local immunohistochemistry 
      showed a 79% agreement rate [kappa statistic, 0.56; 95% confidence interval (95% 
      CI), 0.52-0.60], with FISH done by the central laboratories. The agreement rate 
      comparing BCIRG central laboratory 10H8-IHC and outside/local laboratory 
      immunohistochemistry was 77.5% (kappa statistic, 0.51; 95% CI, 0.46-0.55). 
      Finally, HER-2 status, determined by unspecified FISH assay methods at 
      outside/local laboratories, showed a 92% agreement rate (kappa statistic, 0.83; 
      95% CI, 0.73-0.93), with FISH done at the BCIRG central laboratories. 
      CONCLUSIONS: Compared with the HER-2 status determined at centralized BCIRG 
      reference laboratories, these results indicate superiority of FISH to accurately 
      and reproducibly assess tumors for the HER-2 alteration at outside/local 
      laboratories for entry to clinical trials.
FAU - Press, Michael F
AU  - Press MF
AD  - Women's Cancers Program, Department of Pathology, Norris Comprehensive Cancer 
      Center, University of Southern California Keck School of Medicine, Los Angeles, 
      CA 89195, USA.
FAU - Sauter, Guido
AU  - Sauter G
FAU - Bernstein, Leslie
AU  - Bernstein L
FAU - Villalobos, Ivonne E
AU  - Villalobos IE
FAU - Mirlacher, Martina
AU  - Mirlacher M
FAU - Zhou, Jian-Yuan
AU  - Zhou JY
FAU - Wardeh, Rooba
AU  - Wardeh R
FAU - Li, Yong-Tian
AU  - Li YT
FAU - Guzman, Roberta
AU  - Guzman R
FAU - Ma, Yanling
AU  - Ma Y
FAU - Sullivan-Halley, Jane
AU  - Sullivan-Halley J
FAU - Santiago, Angela
AU  - Santiago A
FAU - Park, Jinha M
AU  - Park JM
FAU - Riva, Alessandro
AU  - Riva A
FAU - Slamon, Dennis J
AU  - Slamon DJ
LA  - eng
GR  - CA48780/CA/NCI NIH HHS/United States
GR  - N01-HD-3-3175/HD/NICHD NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
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 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Biomarkers, Tumor/analysis/genetics
MH  - Breast Neoplasms/*drug therapy/genetics/metabolism
MH  - Cohort Studies
MH  - Female
MH  - Humans
MH  - Immunohistochemistry/methods/standards
MH  - In Situ Hybridization, Fluorescence/methods/standards
MH  - Multicenter Studies as Topic
MH  - Predictive Value of Tests
MH  - Prospective Studies
MH  - Randomized Controlled Trials as Topic
MH  - Receptor, ErbB-2/analysis/*genetics
MH  - Reproducibility of Results
MH  - Treatment Outcome
EDAT- 2005/09/17 09:00
MHDA- 2005/11/09 09:00
CRDT- 2005/09/17 09:00
PHST- 2005/09/17 09:00 [pubmed]
PHST- 2005/11/09 09:00 [medline]
PHST- 2005/09/17 09:00 [entrez]
AID - 11/18/6598 [pii]
AID - 10.1158/1078-0432.CCR-05-0636 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2005 Sep 15;11(18):6598-607. doi: 10.1158/1078-0432.CCR-05-0636.