PMID- 18437174
OWN - NLM
STAT- MEDLINE
DCOM- 20080715
LR  - 20230210
IS  - 0893-3952 (Print)
IS  - 0893-3952 (Linking)
VI  - 21 Suppl 2
DP  - 2008 May
TI  - Current issues in ER and HER2 testing by IHC in breast cancer.
PG  - S8-S15
LID - 10.1038/modpathol.2008.34 [doi]
AB  - The presence of estrogen receptors (ERs), as detected by immunohistochemistry 
      (IHC), is a weak prognostic marker of clinical outcome in breast cancer, but a 
      strong predictive marker for response, for example, to tamoxifen-based therapy. 
      As with all IHC markers, factors such as tissue fixation (both type and 
      duration), the choice of antibody, and the threshold for interpretation of 
      positive immunostaining can dramatically affect test accuracy and 
      reproducibility. For example, optimal fixation for detection of ER requires at 
      least 6-8 h in formalin, and the use of newer antibodies such as SP1 may identify 
      additional patients who might benefit from hormonal therapy. Although the 
      threshold for positivity may be as few as 1% of tumor cells showing nuclear 
      signal, recent studies appear to demonstrate a dichotomization of ER IHC, with 
      the vast majority of cases showing all positive or all negative results. This may 
      be helpful in dictating the appropriateness of hormonal therapy, but 
      quantification of ER by IHC, or other methods, may play a more important role in 
      the future. Breast cancers with human epidermal receptor protein-2 (c-erbB-2; 
      HER2) alterations are critical to identify because such tumors require unique 
      treatment, including the use of targeted therapies such as trastuzumab. HER2 
      alterations at the DNA (amplification) and protein (overexpression) level usually 
      occur in concert, and both fluorescence in situ hybridization (FISH) or IHC can 
      be accurate methods to assess these alterations. However, recent studies have 
      suggested that serious reproducibility issues exist in both FISH and IHC HER2 
      studies. To address this, a joint committee of both the American Society for 
      Clinical Oncologists and the College of American Pathologists has promulgated new 
      guidelines for HER2 testing. These include the following: (a) recommendations for 
      tissue fixation for more than 6 and less than 48 h; (b) new scoring criteria, 
      including a new threshold of 30% strong immunostaining for classification of 3+; 
      (c) introduction of the term 'equivocal' to characterize HER2 studies that are 2+ 
      by IHC and/or show HER2/chromosome 17 ratios of between 1.8 and 2.2 by FISH; (d) 
      requirements for laboratories to validate HER2 assays, generally through the 
      cross-testing of cases with another HER2 methodology, with laboratories required 
      to attain 95% concordance for both positive and negative tests; (e) participation 
      in HER2 proficiency testing.
FAU - Gown, Allen M
AU  - Gown AM
AD  - PhenoPath Laboratories, Seattle, WA 98103, USA. gown@phenopath.com
LA  - eng
PT  - Journal Article
PT  - Review
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  - 0 (Biomarkers, Tumor)
RN  - 0 (Receptors, Estrogen)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Biomarkers, Tumor/*analysis
MH  - Breast Neoplasms/*diagnosis
MH  - Female
MH  - Guidelines as Topic
MH  - Humans
MH  - *Immunohistochemistry/methods
MH  - Receptor, ErbB-2/*analysis
MH  - Receptors, Estrogen/*analysis
MH  - Sensitivity and Specificity
MH  - Tissue Fixation
RF  - 71
EDAT- 2008/06/24 09:00
MHDA- 2008/07/17 09:00
CRDT- 2008/06/24 09:00
PHST- 2008/06/24 09:00 [pubmed]
PHST- 2008/07/17 09:00 [medline]
PHST- 2008/06/24 09:00 [entrez]
AID - S0893-3952(22)02352-3 [pii]
AID - 10.1038/modpathol.2008.34 [doi]
PST - ppublish
SO  - Mod Pathol. 2008 May;21 Suppl 2:S8-S15. doi: 10.1038/modpathol.2008.34.