PMID- 15113815
OWN - NLM
STAT- MEDLINE
DCOM- 20040430
LR  - 20220420
IS  - 1538-3598 (Electronic)
IS  - 0098-7484 (Linking)
VI  - 291
IP  - 16
DP  - 2004 Apr 28
TI  - HER-2 testing in breast cancer using parallel tissue-based methods.
PG  - 1972-7
AB  - CONTEXT: Testing for HER-2 oncogene in breast cancer has increased because of its 
      role as a prognostic and predictive factor. Some advocate gene testing by 
      fluorescence in situ hybridization (FISH) vs protein testing by 
      immunohistochemistry as the method which most accurately evaluates and predicts 
      response to the anti-HER-2 antibody, trastuzumab. However, critical examination 
      of FISH on a screening basis has yet to be performed. OBJECTIVES: To determine 
      the correlation between FISH and immunohistochemistry results by determining 
      HER-2/neu gene status on tumor sections with indeterminate immunohistochemistry 
      results (2+ score), confirm gene amplification on tumor sections with positive 
      results (3+ score), and verify gene status on tumor sections with negative 
      results (0 or 1+ score). DESIGN, SETTING, AND PATIENTS: A quality control and 
      quality assurance program for HER-2 testing by FISH, which used tumor specimens 
      from 2963 patients (median age, 56 years) with breast cancer received from 135 
      hospitals and cancer centers in 29 states, was performed at a reference 
      laboratory from January 1, 1999, to May 15, 2003. Every specimen evaluated by 
      FISH was parallel tested with immunohistochemistry tests. MAIN OUTCOME MEASURES: 
      With FISH as the presumed standard testing method, the positive and negative 
      predictive values and sensitivity and specificity of immunohistochemistry were 
      calculated. RESULTS: A total of 3260 clinical HER-2 tests by FISH were performed 
      on 2963 serially referred breast cancer specimens. Of these, 2933 tests were 
      successful and 2913 breast cancer specimens had both FISH and 
      immunohistochemistry results available. With FISH as the standard testing method, 
      the positive predictive value of positive immunohistochemistry score (3+) was 
      91.6%, and the negative predictive value of negative immunohistochemistry score 
      (0 or 1+) was 97.2%. The sensitivity of immunohistochemistry tests, including 
      tumor sections with scores of 2+ or 3+, was 92.6% and the specificity of 
      immunohistochemistry tests with scores of 3+ was 98.8%. The FISH test had a 
      significantly higher failure rate (5% vs 0.08%) and reagent cost (140 dollars vs 
      10 dollars), and longer testing (36 hours vs 4 hours) and interpretation times (7 
      minutes vs 45 seconds) vs immunohistochemistry tests. CONCLUSIONS: A testing 
      algorithm for HER-2 determination is most efficient by using immunohistochemistry 
      as the method of choice, with FISH performed for cancers with indeterminate 
      results (2+ score). Successful quality control and quality assurance programs are 
      a prerequisite for such approaches.
FAU - Yaziji, Hadi
AU  - Yaziji H
AD  - PhenoPath Laboratories, Seattle, Wash 98103, USA.
FAU - Goldstein, Lynn C
AU  - Goldstein LC
FAU - Barry, Todd S
AU  - Barry TS
FAU - Werling, Robert
AU  - Werling R
FAU - Hwang, Harry
AU  - Hwang H
FAU - Ellis, Georgiana K
AU  - Ellis GK
FAU - Gralow, Julie R
AU  - Gralow JR
FAU - Livingston, Robert B
AU  - Livingston RB
FAU - Gown, Allen M
AU  - Gown AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - JAMA
JT  - JAMA
JID - 7501160
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
CIN - JAMA. 2004 Apr 28;291(16):2019-20. PMID: 15113823
CIN - JAMA. 2004 Jul 21;292(3):328; author reply 328-9. PMID: 15265845
CIN - JAMA. 2004 Oct 20;292(15):1817-8; author reply 1818. PMID: 15494577
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Algorithms
MH  - Antibodies, Monoclonal/therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/therapeutic use
MH  - Breast Neoplasms/drug therapy/*genetics/metabolism/pathology
MH  - *Genes, erbB-2
MH  - Genetic Testing/methods/standards
MH  - Humans
MH  - *Immunohistochemistry/standards
MH  - *In Situ Hybridization, Fluorescence/standards
MH  - Middle Aged
MH  - Predictive Value of Tests
MH  - Quality Control
MH  - Receptor, ErbB-2/*metabolism
MH  - Sensitivity and Specificity
MH  - Trastuzumab
EDAT- 2004/04/29 05:00
MHDA- 2004/05/01 05:00
CRDT- 2004/04/29 05:00
PHST- 2004/04/29 05:00 [pubmed]
PHST- 2004/05/01 05:00 [medline]
PHST- 2004/04/29 05:00 [entrez]
AID - 291/16/1972 [pii]
AID - 10.1001/jama.291.16.1972 [doi]
PST - ppublish
SO  - JAMA. 2004 Apr 28;291(16):1972-7. doi: 10.1001/jama.291.16.1972.