PMID- 20665045
OWN - NLM
STAT- MEDLINE
DCOM- 20100928
LR  - 20211020
IS  - 1432-2307 (Electronic)
IS  - 0945-6317 (Print)
IS  - 0945-6317 (Linking)
VI  - 457
IP  - 3
DP  - 2010 Sep
TI  - HER2 diagnostics in gastric cancer-guideline validation and development of 
      standardized immunohistochemical testing.
PG  - 299-307
LID - 10.1007/s00428-010-0952-2 [doi]
AB  - Trastuzumab-based therapy has been shown to confer overall survival benefit in 
      HER2-positive patients with advanced gastric cancer in a large multicentric trial 
      (ToGA study). Subgroup analysis identified adenocarcinomas of the stomach and 
      gastroesophageal (GE) junction with overexpression of HER2 according to 
      immunohistochemistry (IHC) as potential responders. Due to recent approval of 
      trastuzumab for HER2 positive metastatic gastric and GE-junction cancer in Europe 
      (EMEA) HER2 diagnostics is now mandatory with IHC being the primary test followed 
      by fluorescence in situ hybridization (FISH) in IHC2+ cases. However, in order to 
      not miss patients potentially responding to targeted therapy determination of a 
      HER2-positive status for gastric cancer required modification of scoring as had 
      been proposed in a pre-ToGA study. To validate this new HER2 status testing 
      procedure in terms of inter-laboratory and inter-observer consensus for IHC 
      scoring a series of 547 gastric cancer tissue samples on a tissue microarray 
      (TMA) was used. In the first step, 30 representative cores were used to identify 
      specific IHC HER2 scoring issues among eight French and German laboratories, 
      while in the second step the full set of 547 cores was used to determine IHC HER2 
      intensity and area score concordance between six German pathologists. Specific 
      issues relating to discordance were identified and recommendations formulated 
      which proved to be effective to reliably determine HER2 status in a prospective 
      test series of 447 diagnostic gastric cancer specimens.
FAU - Ruschoff, Josef
AU  - Ruschoff J
AD  - Targos Molecular Pathology GmbH und Pathologie Nordhessen, 34119 Kassel, Germany. 
      rueschoff@patho-nordhessen.de
FAU - Dietel, Manfred
AU  - Dietel M
FAU - Baretton, Gustavo
AU  - Baretton G
FAU - Arbogast, Susanne
AU  - Arbogast S
FAU - Walch, Axel
AU  - Walch A
FAU - Monges, Genevieve
AU  - Monges G
FAU - Chenard, Marie-Pierre
AU  - Chenard MP
FAU - Penault-Llorca, Frederique
AU  - Penault-Llorca F
FAU - Nagelmeier, Iris
AU  - Nagelmeier I
FAU - Schlake, Werner
AU  - Schlake W
FAU - Hofler, H
AU  - Hofler H
FAU - Kreipe, H H
AU  - Kreipe HH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
DEP - 20100728
PL  - Germany
TA  - Virchows Arch
JT  - Virchows Archiv : an international journal of pathology
JID - 9423843
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Biomarkers, Tumor/analysis/genetics
MH  - Humans
MH  - Immunohistochemistry/methods/*standards
MH  - Observer Variation
MH  - Practice Guidelines as Topic
MH  - Receptor, ErbB-2/*analysis/genetics
MH  - Reproducibility of Results
MH  - Stomach Neoplasms/epidemiology/*genetics
MH  - Tissue Array Analysis
PMC - PMC2933810
EDAT- 2010/07/29 06:00
MHDA- 2010/09/30 06:00
PMCR- 2010/07/28
CRDT- 2010/07/29 06:00
PHST- 2009/11/10 00:00 [received]
PHST- 2010/07/13 00:00 [accepted]
PHST- 2010/07/02 00:00 [revised]
PHST- 2010/07/29 06:00 [entrez]
PHST- 2010/07/29 06:00 [pubmed]
PHST- 2010/09/30 06:00 [medline]
PHST- 2010/07/28 00:00 [pmc-release]
AID - 952 [pii]
AID - 10.1007/s00428-010-0952-2 [doi]
PST - ppublish
SO  - Virchows Arch. 2010 Sep;457(3):299-307. doi: 10.1007/s00428-010-0952-2. Epub 2010 
      Jul 28.