PMID- 11054438
OWN - NLM
STAT- MEDLINE
DCOM- 20001130
LR  - 20191210
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 18
IP  - 21
DP  - 2000 Nov 1
TI  - Assessment of methods for tissue-based detection of the HER-2/neu alteration in 
      human breast cancer: a direct comparison of fluorescence in situ hybridization 
      and immunohistochemistry.
PG  - 3651-64
AB  - PURPOSE: To compare the efficacy of fluorescence in situ hybridization (FISH) and 
      immunohistochemistry (IHC) in detecting the HER-2/neu alteration in human breast 
      cancer. PATIENTS AND METHODS: Unselected stage I, II, and III breast cancer 
      patients (N = 900) were tested for HER-2/neu gene amplification by FISH in 
      paraffin-embedded, formalin-fixed archival material. Of these samples, 856 were 
      tested for HER-2/neu overexpression by non-antigen-retrieval IHC with the 
      polyclonal antibody R60, the sensitivity and specificity of which was 
      preliminarily compared with the United States Food and Drug 
      Administration-approved HercepTest (Dako Corp, Carpinteria, CA). Patient survival 
      was analyzed in relation to the presence of the HER-2/neu alteration as 
      determined by these two methodologies. RESULTS: A total of 189 (21%) of 900 
      patients were positive by FISH and 147 (17.2%) of 856 were positive by IHC. This 
      discrepancy is consistent with expected loss of IHC sensitivity associated with 
      tissue fixation/embedding. The HercepTest did not improve sensitivity and 
      introduced false positives. Comparison of R60-based IHC with FISH demonstrates 
      that patient survival is associated progressively to gene amplification level as 
      determined by FISH, whereas for IHC an association is found only in the highest 
      (3+) immunostaining group. Among FISH-negative tumors, 45 (6.6%) of 678 were 
      IHC-positive, with a survival probability similar to that of 
      FISH-negative/IHC-negative cases; FISH-positive/IHC-negative patients have a 
      survival probability similar to that of FISH-positive/IHC-positive cases. 
      CONCLUSION: IHC does not consistently discriminate patients likely to have a poor 
      prognosis, whereas FISH provides superior prognostic information in segregating 
      high-risk from lower-risk beast cancers. HER-2/neu protein overexpression in the 
      absence of gene amplification occurs infrequently in breast cancer, in which 
      case, patient outcome is similar to that of patients without the alteration.
FAU - Pauletti, G
AU  - Pauletti G
AD  - Department of Medicine, Division of Hematology-Oncology, University of California 
      at Los Angeles, UCLA School of Medicine, Los Angeles, CA, USA.
FAU - Dandekar, S
AU  - Dandekar S
FAU - Rong, H
AU  - Rong H
FAU - Ramos, L
AU  - Ramos L
FAU - Peng, H
AU  - Peng H
FAU - Seshadri, R
AU  - Seshadri R
FAU - Slamon, D J
AU  - Slamon DJ
LA  - eng
PT  - Comparative Study
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 1HG84L3525 (Formaldehyde)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
CIN - Adv Anat Pathol. 2002 Nov;9(6):338-44. PMID: 12409642
MH  - Adult
MH  - Breast Neoplasms/*genetics/*metabolism
MH  - Female
MH  - Formaldehyde
MH  - Gene Amplification
MH  - Gene Expression
MH  - *Genes, erbB-2
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Paraffin Embedding
MH  - Predictive Value of Tests
MH  - Receptor, ErbB-2/*biosynthesis/genetics
MH  - Sensitivity and Specificity
MH  - Survival Analysis
MH  - Tissue Fixation
EDAT- 2000/10/31 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/31 11:00
PHST- 2000/10/31 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/31 11:00 [entrez]
AID - 10.1200/JCO.2000.18.21.3651 [doi]
PST - ppublish
SO  - J Clin Oncol. 2000 Nov 1;18(21):3651-64. doi: 10.1200/JCO.2000.18.21.3651.