PMID- 10955453
OWN - NLM
STAT- MEDLINE
DCOM- 20001207
LR  - 20220409
IS  - 0893-3952 (Print)
IS  - 0893-3952 (Linking)
VI  - 13
IP  - 8
DP  - 2000 Aug
TI  - HER-2/neu testing in breast carcinoma: a combined immunohistochemical and 
      fluorescence in situ hybridization approach.
PG  - 866-73
AB  - We evaluated 750 consecutive invasive breast carcinomas for HER-2/neu utilizing a 
      combination of immunohistochemical (IHC) and fluorescence in situ hybridization 
      (FISH) methodologies. IHC reactions of 3+ were considered HER-2/neu positive and 
      0 and 1+ IHC reactions were considered HER-2/neu negative. IHC reactions of 2+ 
      were considered inconclusive and reflexed to FISH analysis. In addition, a 10% 
      sampling and validation FISH analysis was performed on the positive and negative 
      IHC tests. One hundred thirty-eight cases (18.4%) were HER-2/neu positive by IHC 
      and/or FISH. One hundred twenty-three of the positive cases (89%) were 3+ IHC 
      reactions and 14 positive cases were inconclusive by IHC and amplified by FISH. 
      There was concordance with FISH in 77 of 78 (98.7%) of the positive or negative 
      IHC cases that were tested (95% confidence interval [CI] = 93.1 to 100%). A 
      single IHC-negative case showed HER-2/neu amplification by FISH. Thirty-nine 
      cases were 2+ IHC (5.2%); 14 (36%) were amplified, 24 (62%) were not amplified, 
      and one was not interpretable. HER-2/neu positivity was observed in 34% of grade 
      3 ductal carcinomas, 11.4% of grade 2 ductal carcinomas, 3.2% of grade 1 ductal 
      carcinomas, and 3.2% of lobular carcinomas. Occasional cases with discordant IHC 
      expression of HER-2/neu within the in situ and invasive carcinoma elements were 
      also identified. IHC reliably characterized HER-2/neu in approximately 95% of the 
      cases studied (95% CI = 93.0 to 96.2%) and was effective as a primary method for 
      evaluating HER-2/neu status. In this study, 2+ IHC reactions were a heterogeneous 
      group best regarded as indeterminate or inconclusive; in this series, only 36% 
      were amplified by FISH analysis. Our findings suggest that a combination of IHC 
      and FISH testing with FISH analysis performed reflexly on all 2+ IHC cases can 
      optimize HER-2/neu testing.
FAU - Ridolfi, R L
AU  - Ridolfi RL
AD  - Southern California Permanente Medical Group, Regional Reference Laboratories, 
      Immunohistochemistry, North Hollywood 91605, USA. ren.l.ridolfi@kp.org
FAU - Jamehdor, M R
AU  - Jamehdor MR
FAU - Arber, J M
AU  - Arber JM
LA  - eng
PT  - Journal Article
PT  - Validation Study
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 (DNA, Neoplasm)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Breast Neoplasms/genetics/*metabolism/pathology
MH  - Carcinoma, Ductal, Breast/genetics/*metabolism/pathology
MH  - Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology
MH  - Carcinoma, Lobular/genetics/*metabolism/pathology
MH  - DNA, Neoplasm/analysis
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Receptor, ErbB-2/genetics/*metabolism
MH  - Reproducibility of Results
EDAT- 2000/08/24 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/08/24 11:00
PHST- 2000/08/24 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/08/24 11:00 [entrez]
AID - 10.1038/modpathol.3880154 [doi]
PST - ppublish
SO  - Mod Pathol. 2000 Aug;13(8):866-73. doi: 10.1038/modpathol.3880154.