PMID- 17396141
OWN - NLM
STAT- MEDLINE
DCOM- 20070706
LR  - 20230210
IS  - 0893-3952 (Print)
IS  - 0893-3952 (Linking)
VI  - 20
IP  - 5
DP  - 2007 May
TI  - Standardization of HER2 testing: results of an international proficiency-testing 
      ring study.
PG  - 584-91
AB  - Human epidermal growth factor receptor 2 (HER2) positivity in breast cancer is a 
      prognostic factor regarding tumor aggressiveness and a predictive factor for 
      response to trastuzumab (Herceptin). Early and accurate HER2 testing of all 
      breast cancer patients at primary diagnosis is essential for optimal disease 
      management. Routine HER2 tests, such as immunohistochemistry and fluorescence in 
      situ hybridization (FISH), are subject to interlaboratory variation, and 
      validation by laboratory proficiency testing is important to improve 
      standardization. This study compared immunohistochemistry and FISH testing 
      between five international pathology reference centers. Each center evaluated 20 
      immunohistochemistry and 20 FISH breast cancer specimens in five testing rounds. 
      In each round, one center selected two sets of four different invasive tumor 
      specimens (set A for immunohistochemistry and set B for FISH) and sent samples to 
      the other four centers in a blinded manner, while retaining samples for its own 
      evaluation. Results were analyzed by an independent coordinator. With 
      immunohistochemistry, there were no differences between the five centers for any 
      of the specimens at the level of diagnostic decision (positive or negative HER2 
      status). However, differences between laboratories were observed in 
      immunohistochemistry scoring. Of the 20 specimens, four were scored as negative 
      (0/1+) and five as positive (3+) in all centers; eight were negative or equivocal 
      (2+), and three positive or equivocal. After FISH retesting of nine of the 11 
      equivocal immunohistochemistry cases, consensus was achieved in 15 of 18 (83%) 
      specimens. FISH analysis of set B specimens resulted in consensus between centers 
      in 16 of 20 (80%) specimens (six negative and 10 positive). All four discordant 
      FISH specimens were scored as having HER2:CEP17 ratios within the range 1.7-2.3 
      by at least one center. Equivocal immunohistochemistry and borderline FISH cases 
      are difficult to interpret, even for highly experienced and validated 
      laboratories, highlighting the need for quality-control procedures.
FAU - Dowsett, Mitch
AU  - Dowsett M
AD  - Academic Depertment of Biochemistry, Royal Marsden Hospital, London, UK. 
      mitch.dowsett@icr.ac.uk
FAU - Hanna, Wedad M
AU  - Hanna WM
FAU - Kockx, Mark
AU  - Kockx M
FAU - Penault-Llorca, Frederique
AU  - Penault-Llorca F
FAU - Ruschoff, Josef
AU  - Ruschoff J
FAU - Gutjahr, Thorsten
AU  - Gutjahr T
FAU - Habben, Kai
AU  - Habben K
FAU - van de Vijver, Marc J
AU  - van de Vijver MJ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
DEP - 20070330
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Algorithms
MH  - Antibodies, Monoclonal/therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/therapeutic use
MH  - Breast Neoplasms/drug therapy/*metabolism
MH  - Female
MH  - Humans
MH  - Immunohistochemistry/*standards
MH  - In Situ Hybridization, Fluorescence/*standards
MH  - Pathology, Clinical/*standards
MH  - Quality Assurance, Health Care
MH  - Receptor, ErbB-2/*metabolism
MH  - Reproducibility of Results
MH  - Trastuzumab
EDAT- 2007/03/31 09:00
MHDA- 2007/07/07 09:00
CRDT- 2007/03/31 09:00
PHST- 2007/03/31 09:00 [pubmed]
PHST- 2007/07/07 09:00 [medline]
PHST- 2007/03/31 09:00 [entrez]
AID - S0893-3952(22)04965-1 [pii]
AID - 10.1038/modpathol.3800774 [doi]
PST - ppublish
SO  - Mod Pathol. 2007 May;20(5):584-91. doi: 10.1038/modpathol.3800774. Epub 2007 Mar 
      30.