PMID- 15077921
OWN - NLM
STAT- MEDLINE
DCOM- 20041021
LR  - 20221007
IS  - 0393-6155 (Print)
IS  - 0393-6155 (Linking)
VI  - 19
IP  - 1
DP  - 2004 Jan-Mar
TI  - Discordant results obtained for different methods of HER-2/neu testing in breast 
      cancer--a question of standardization, automation and timing.
PG  - 1-13
AB  - BACKGROUND: HER-2/neu positivity is required for the selection of stage IV breast 
      cancer patients for trastuzumab therapy. We compared the results of the 
      recommended immunohistochemistry (IHC) evaluation with the automated ACIS IHC 
      system and with fluorescence in situ hybridization (FISH). These HER-2/neu tissue 
      results were correlated with the serum HER-2/neu (sHER-2/neu) levels at the time 
      of metastatic spread. PATIENTS AND METHODS: A total of 61 IHC slides from 30 
      patients were stained using the HercepTest. HER-2/neu gene amplification was 
      determined using the Ventana FISH assay. sHER-2/neu levels were measured with the 
      Oncogene Science" ELISA kit. The concordance of HER-2/neu results was determined 
      using the concordance index Kappa (kappa). RESULTS: The best concordance between 
      any IHC and FISH was found for the automated ACIS system (88.5%, kappa=0.68, 
      category "good"). The comparison between the manual interpretations and the 
      automated IHC was categorized as "very good" (95.1%, kappa=0.85). The median 
      sHER-2/neu level of FISH positive patients was significantly higher (67 ng/mL) 
      than that of FISH negative patients (17 ng/mL, p=0.018). The increase in 
      HER-2/neu positivity comparing tissue to stage IV serum was statistically 
      significant (p=0.001). CONCLUSIONS: The concordance between conventional IHC and 
      computerized analysis was very good. The number of patients with stage IV breast 
      cancer with an elevated sHER-2/neu level was much higher than HER-2/neu 
      positivity in tissue. This discrepancy is only partially explained by the 
      influence of tumor load. Patients with an elevated sHER-2/neu level and no tissue 
      overexpression should be considered for retesting of tissue or a new biopsy.
FAU - Luftner, D
AU  - Luftner D
AD  - Medizinische Klinik und Poliklinik II, Schwerpunkt Onkologie und Hamatologie, 
      Universitatsklinikum Charite, Humboldt-Universitat, Berlin, Germany. 
      Diana.Lueftner@rz.hu-berlin.de
FAU - Henschke, P
AU  - Henschke P
FAU - Kafka, A
AU  - Kafka A
FAU - Anagnostopoulos, I
AU  - Anagnostopoulos I
FAU - Wiechen, K
AU  - Wiechen K
FAU - Geppert, R
AU  - Geppert R
FAU - Stein, H
AU  - Stein H
FAU - Wernecke, K D
AU  - Wernecke KD
FAU - Kreienberg, R
AU  - Kreienberg R
FAU - Possinger, K
AU  - Possinger K
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Int J Biol Markers
JT  - The International journal of biological markers
JID - 8712411
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Biomarkers, Tumor/biosynthesis/*blood
MH  - Breast Neoplasms/*diagnosis/*genetics
MH  - Disease Progression
MH  - Enzyme-Linked Immunosorbent Assay
MH  - *Genetic Predisposition to Disease
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Mass Screening/*methods/*standards
MH  - Receptor, ErbB-2/*blood/*genetics
MH  - Reproducibility of Results
MH  - Time Factors
EDAT- 2004/04/14 05:00
MHDA- 2004/10/22 09:00
CRDT- 2004/04/14 05:00
PHST- 2004/04/14 05:00 [pubmed]
PHST- 2004/10/22 09:00 [medline]
PHST- 2004/04/14 05:00 [entrez]
AID - 10.1177/172460080401900101 [doi]
PST - ppublish
SO  - Int J Biol Markers. 2004 Jan-Mar;19(1):1-13. doi: 10.1177/172460080401900101.