PMID- 11774167
OWN - NLM
STAT- MEDLINE
DCOM- 20020125
LR  - 20141120
IS  - 0046-8177 (Print)
IS  - 0046-8177 (Linking)
VI  - 32
IP  - 12
DP  - 2001 Dec
TI  - Tyrosine kinase activation in breast carcinoma with correlation to HER-2/neu gene 
      amplification and receptor overexpression.
PG  - 1344-50
AB  - The HER-2/neu oncogene encodes a transmembrane receptor with intrinsic tyrosine 
      kinase activity. A pilot study was performed to investigate downstream effects of 
      HER-2/neu (or related growth factor receptor) activation by identifying 
      phosphorylated tyrosine. Fifty-four breast carcinomas were evaluated for 
      HER-2/neu overexpression by the HercepTest (Dako, Carpinteria, CA) and the 
      monoclonal CB11 antibody (Ventana, Tucson, AZ). Phosphotyrosine (an indication of 
      tyrosine kinase activity) was detected by an antiphosphotyrosine mouse monoclonal 
      antibody (Upstate Biotechnology, Lake Placid, NY). The gene amplification status 
      was evaluated in 50 of the 54 cases by fluorescence in situ hybridization (FISH) 
      using the Ventana gene probe. The HER-2/neu oncogene amplification was detected 
      in 28% (14 of 50) of cases. Of the 14 cases showing oncogene amplification, 
      tyrosine kinase activity was detected in 9 (64.2%) cases. There was moderate 
      agreement between HER-2/neu gene amplification and tyrosine kinase activity 
      (kappa = 0.43). Immunohistochemical staining of 3+ (with both HercepTest and 
      CB11) showed better agreement with HER-2/neu oncogene amplification and increased 
      tyrosine kinase activity than 2+ immunohistochemical staining. Overall, oncogene 
      amplification and overexpression correlated with increased tyrosine kinase 
      activity, supporting the mechanism of tyrosine kinase activation by HER-2/neu 
      amplification and overexpression. However, 7 cases showing increased tyrosine 
      kinase activity did not show gene amplification or 3+ receptor expression (by 
      either HercepTest or CB11), raising the possibility of other growth factor 
      receptors operating via the tyrosine kinase pathway. There was no apparent 
      correlation between tyrosine kinase activity and hormone receptor status 
      (estrogen or progesterone). Increased tyrosine kinase activity is more commonly 
      associated with higher-grade tumors and thus may correlate with aggressive 
      biologic behavior in breast carcinoma. The results of this pilot study suggest 
      that a larger-scale investigation into downstream activation of tyrosine kinase 
      and correlation to clinical outcome or response to Herceptin therapy may identify 
      subsets of patients whose clinical response or outcome may be predicted by 
      tyrosine kinase activation.
CI  - Copyright 2001 by W.B. Saunders Company
FAU - Bhargava, R
AU  - Bhargava R
AD  - Department of Pathology, Baystate Medical Center, Springfield, MA 01199, USA.
FAU - Naeem, R
AU  - Naeem R
FAU - Marconi, S
AU  - Marconi S
FAU - Luszcz, J
AU  - Luszcz J
FAU - Garb, J
AU  - Garb J
FAU - Gasparini, R
AU  - Gasparini R
FAU - Otis, C N
AU  - Otis CN
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Hum Pathol
JT  - Human pathology
JID - 9421547
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, Progesterone)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Breast Neoplasms/*enzymology/*genetics/pathology/surgery
MH  - Enzyme Activation
MH  - Female
MH  - Gene Amplification
MH  - Genes, erbB-2/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lymph Nodes/pathology
MH  - Lymphatic Metastasis
MH  - Middle Aged
MH  - Pilot Projects
MH  - Prognosis
MH  - Protein-Tyrosine Kinases/*biosynthesis
MH  - Receptor, ErbB-2/biosynthesis/*genetics
MH  - Receptors, Estrogen/metabolism
MH  - Receptors, Progesterone/metabolism
EDAT- 2002/01/05 10:00
MHDA- 2002/01/26 10:01
CRDT- 2002/01/05 10:00
PHST- 2002/01/05 10:00 [pubmed]
PHST- 2002/01/26 10:01 [medline]
PHST- 2002/01/05 10:00 [entrez]
AID - S0046-8177(01)62921-6 [pii]
AID - 10.1053/hupa.2001.29668 [doi]
PST - ppublish
SO  - Hum Pathol. 2001 Dec;32(12):1344-50. doi: 10.1053/hupa.2001.29668.