PMID- 15163239
OWN - NLM
STAT- MEDLINE
DCOM- 20041012
LR  - 20210527
IS  - 1543-2165 (Electronic)
IS  - 0003-9985 (Linking)
VI  - 128
IP  - 6
DP  - 2004 Jun
TI  - Comparative assays for the HER-2/neu oncogene status in breast cancer.
PG  - 627-33
AB  - CONTEXT: Tumor marker assays, especially those used to indicate the right 
      therapy, should be standardized. OBJECTIVE: To analyze the current methods for 
      the HER-2/neu (h2n) oncogene status by immunohistochemical (IHC) analysis, 
      fluorescence in situ hybridization (FISH), and chromogenic in situ hybridization 
      (CISH) and compare those results with the chromosome 17 copy number and the 
      status of the topoisomerase II alpha (TPIIalpha) gene. DESIGN: We tested 50 
      infiltrating ductal breast carcinomas (pTNM status varied from pT1 N0 to pT4 N1) 
      using the Food and Drug Administration (FDA)-approved methods HercepTest and 
      Pathway for overexpression of h2n. We also used FISH and CISH to test for h2n 
      amplification and CISH to test for chromosome 17 (c17) and TPIIalpha. The p53 and 
      Ki-67 factors were also evaluated by IHC analysis. RESULTS: h2n overexpression 
      (3+) and amplification were observed in only 6 (12%) of 50 cases by IHC analysis, 
      FISH, and CISH. Three cases that initially scored 3+ and 2+ had 4 to 5.95 signals 
      (equivocal) by FISH but when corrected by the h2n/c17 ratio were nonamplified. 
      TPIIalpha isomerase was amplified in only 2 (4%) of the 50 cases. Nineteen (38%) 
      of the 50 cases were aneuploidic. All h2n amplified cases had high proliferative 
      activity, but only 2 of 6 had p53 protein alterations. CONCLUSIONS: The 
      HercepTest and Pathway IHC assay h2n were fully concordant for the 3+ cases. The 
      3+ cases had to be confirmed in 75% of the tumor area examined. These 2 IHC 
      assays were fully concordant with FISH and CISH. The 2 in situ hybridization 
      (ISH) assays were 94% concordant for the 50 cases. The cutoff signal points for 
      both ISH assays should be 6 or more. Thus, there is no need for the c17 ratio 
      correction. Tumor heterogeneity appears not be a major problem, but our 
      percentage of amplified cases is lower than previously reported. The FDA-approved 
      IHC and ISH assays should give relatively uniform results when used following our 
      recommendations.
FAU - Vera-Roman, Jose Maria
AU  - Vera-Roman JM
AD  - Department of Pathology, Hospital General de Castellon, Castellon de la Plana, 
      Spain. vera_jos@gva.es
FAU - Rubio-Martinez, Luis Alberto
AU  - Rubio-Martinez LA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Arch Pathol Lab Med
JT  - Archives of pathology & laboratory medicine
JID - 7607091
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Chromogenic Compounds)
RN  - 0 (DNA-Binding Proteins)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 5.99.1.3 (DNA Topoisomerases, Type II)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antigens, Neoplasm
MH  - Breast Neoplasms/*diagnosis
MH  - Carcinoma, Ductal, Breast/*diagnosis
MH  - Chromogenic Compounds
MH  - Chromosomes, Human, Pair 17
MH  - DNA Topoisomerases, Type II/genetics
MH  - DNA-Binding Proteins
MH  - Female
MH  - Gene Dosage
MH  - *Genes, erbB-2
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - Receptor, ErbB-2/*analysis
EDAT- 2004/05/28 05:00
MHDA- 2004/10/13 09:00
CRDT- 2004/05/28 05:00
PHST- 2004/05/28 05:00 [pubmed]
PHST- 2004/10/13 09:00 [medline]
PHST- 2004/05/28 05:00 [entrez]
AID - OA3178 [pii]
AID - 10.5858/2004-128-627-CAFTNO [doi]
PST - ppublish
SO  - Arch Pathol Lab Med. 2004 Jun;128(6):627-33. doi: 10.5858/2004-128-627-CAFTNO.