PMID- 22282306
OWN - NLM
STAT- MEDLINE
DCOM- 20120823
LR  - 20230210
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 25
IP  - 5
DP  - 2012 May
TI  - 'Genetic heterogeneity' in HER2/neu testing by fluorescence in situ 
      hybridization: a study of 2,522 cases.
PG  - 683-8
LID - 10.1038/modpathol.2011.206 [doi]
AB  - Amplification for the ERBB2 oncogene encoding the HER2/neu protein (HER2) is of 
      predictive and prognostic importance in breast carcinoma. Fluorescence in situ 
      hybridization (FISH) is a widely accepted method for determining HER2 
      amplification status. A HER2-amplified tumor is defined as having a ratio of HER2 
      signals to chromosome 17 centromeric probe signals (HER2/CEP17 ratio) exceeding 
      2.2. However, the presence of scattered cells demonstrating HER2 amplification is 
      of unclear significance. A 2009 panel guideline defined a tumor with 'genetic 
      heterogeneity' as having at least 5% but fewer than 50% of (non-clustered) tumor 
      nuclei with a ratio >2.2. The study objective was to examine the statistical 
      distribution of breast tumors tested by FISH for HER2 amplification, after 
      implementation of this 2009 guideline. We identified 2522 consecutive breast 
      carcinoma cases (2009-2011) tested for HER2 amplification. All cases were tested 
      by FISH using a standard clinical protocol, adhering to established guidelines. 
      For each case, data on cell counts were retrieved electronically. Each tumor was 
      compared with a theoretical normal distribution by quantile-quantile analysis. Of 
      2522 FISH tests for HER2, 1900 (75%) were non-amplified, 394 (16%) were 
      amplified, and 228 (9%) were HER2-equivocal. A total of 666 (26%) had 'genetic 
      heterogeneity.' Among these 'genetically heterogeneous' cases, the ratio was 
      non-amplified in 430 (64.5%), amplified in 24 (4%), and equivocal in 212 (31.5%). 
      The amplified subpopulation in 'genetically heterogeneous' tumors was larger if 
      the overall ratio was close to 2.2. However, the percentage of nuclei >2.2 in a 
      'genetically heterogeneous' tumor was not informative of the underlying 
      tumor-cell distribution. We conclude that the proportion of HER2-amplified nuclei 
      within a tumor does not contribute information independent of the actual 
      HER2/CEP17 ratio. Reassessment of the definition of 'genetic heterogeneity' in 
      HER2 testing is warranted.
FAU - Chang, Martin C
AU  - Chang MC
AD  - Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, 
      ON, Canada. mchang2@mtsinai.on.ca
FAU - Malowany, Janet I
AU  - Malowany JI
FAU - Mazurkiewicz, Julita
AU  - Mazurkiewicz J
FAU - Wood, Martha
AU  - Wood M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120127
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  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adenocarcinoma/*diagnosis/genetics
MH  - Breast Neoplasms/*diagnosis/genetics
MH  - Female
MH  - Gene Amplification
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Prognosis
MH  - Receptor, ErbB-2/*genetics
EDAT- 2012/01/28 06:00
MHDA- 2012/08/24 06:00
CRDT- 2012/01/28 06:00
PHST- 2012/01/28 06:00 [entrez]
PHST- 2012/01/28 06:00 [pubmed]
PHST- 2012/08/24 06:00 [medline]
AID - S0893-3952(22)01616-7 [pii]
AID - 10.1038/modpathol.2011.206 [doi]
PST - ppublish
SO  - Mod Pathol. 2012 May;25(5):683-8. doi: 10.1038/modpathol.2011.206. Epub 2012 Jan 
      27.