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Relationship between pathological features, HER2 protein expression and HER2 and CEP17 copy number in breast cancer: biological and methodological considerations

Kathleen Lambein UGent, Marleen Praet UGent, Ramses Forsyth UGent, Rudy Van den Broecke UGent, Geert Braems UGent, BART MATTHYS UGent, Veronique Cocquyt UGent, Hannelore Denys UGent, Patrick Pauwels UGent and Louis Libbrecht UGent (2011) JOURNAL OF CLINICAL PATHOLOGY. 64(3). p.200-207
abstract
Aims A few reports have assessed HER2 status in breast cancer by both dual-probe fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in an unselected and consecutive fashion, but CEP17 and HER2 copy number were not evaluated separately in these studies. Therefore, the aim of this study was to perform FISH testing for HER2 in a large number of breast tumours, irrespective of the IHC scores, which were also determined in all cases. Methods Both FISH and IHC were applied to 200 tumours from 196 consecutive patients who underwent resection of primary breast cancer with the sentinel procedure and/or axillary dissection. Not only the ratio, but also mean HER2 and CEP17 copy number were determined and used in statistical analyses to evaluate relationships between FISH, IHC and clinicopathological features. Results The amplification status based solely on HER2 signals was 98% concordant with results of dual-probe FISH. In non-amplified tumours, the mean CEP17 and HER2 copy number correlated, possibly because of cell cycling. Amplified tumours were histopathologically more aggressive than non-amplified tumours, and features of aggressiveness increased with the mean HER2 copy number. In both amplified and non-amplified tumours, a gene dosage effect was observed: an increase in the mean HER2 copy number was associated with a higher IHC score. Conclusions This working method and analysis enabled new insights to be obtained into the pathobiology of HER2 in breast cancer. The findings may be helpful in optimising the methodology of HER2 testing.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
RECEPTOR 2 ASSESSMENT, IN-SITU HYBRIDIZATION, SURVIVAL, TRIAL, GUIDELINES, POLYSOMY, TRASTUZUMAB, AMPLIFICATION, GENETIC-HETEROGENEITY, ADJUVANT CHEMOTHERAPY
journal title
JOURNAL OF CLINICAL PATHOLOGY
J. Clin. Pathol.
volume
64
issue
3
pages
200 - 207
Web of Science type
Article
Web of Science id
000287442300003
JCR category
PATHOLOGY
JCR impact factor
2.306 (2011)
JCR rank
32/78 (2011)
JCR quartile
2 (2011)
ISSN
0021-9746
DOI
10.1136/jcp.2010.084863
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1619009
handle
http://hdl.handle.net/1854/LU-1619009
date created
2011-06-27 14:52:36
date last changed
2012-03-22 15:30:29
@article{1619009,
  abstract     = {Aims A few reports have assessed HER2 status in breast cancer by both dual-probe fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in an unselected and consecutive fashion, but CEP17 and HER2 copy number were not evaluated separately in these studies. Therefore, the aim of this study was to perform FISH testing for HER2 in a large number of breast tumours, irrespective of the IHC scores, which were also determined in all cases.
Methods Both FISH and IHC were applied to 200 tumours from 196 consecutive patients who underwent resection of primary breast cancer with the sentinel procedure and/or axillary dissection. Not only the ratio, but also mean HER2 and CEP17 copy number were determined and used in statistical analyses to evaluate relationships between FISH, IHC and clinicopathological features.
Results The amplification status based solely on HER2 signals was 98\% concordant with results of dual-probe FISH. In non-amplified tumours, the mean CEP17 and HER2 copy number correlated, possibly because of cell cycling. Amplified tumours were histopathologically more aggressive than non-amplified tumours, and features of aggressiveness increased with the mean HER2 copy number. In both amplified and non-amplified tumours, a gene dosage effect was observed: an increase in the mean HER2 copy number was associated with a higher IHC score.
Conclusions This working method and analysis enabled new insights to be obtained into the pathobiology of HER2 in breast cancer. The findings may be helpful in optimising the methodology of HER2 testing.},
  author       = {Lambein, Kathleen and Praet, Marleen and Forsyth, Ramses and Van den Broecke, Rudy and Braems, Geert and MATTHYS, BART and Cocquyt, Veronique and Denys, Hannelore and Pauwels, Patrick and Libbrecht, Louis},
  issn         = {0021-9746},
  journal      = {JOURNAL OF CLINICAL PATHOLOGY},
  keyword      = {RECEPTOR 2 ASSESSMENT,IN-SITU HYBRIDIZATION,SURVIVAL,TRIAL,GUIDELINES,POLYSOMY,TRASTUZUMAB,AMPLIFICATION,GENETIC-HETEROGENEITY,ADJUVANT CHEMOTHERAPY},
  language     = {eng},
  number       = {3},
  pages        = {200--207},
  title        = {Relationship between pathological features, HER2 protein expression and HER2 and CEP17 copy number in breast cancer: biological and methodological considerations},
  url          = {http://dx.doi.org/10.1136/jcp.2010.084863},
  volume       = {64},
  year         = {2011},
}

Chicago
Lambein, Kathleen, Marleen Praet, Ramses Forsyth, Rudy Van den Broecke, Geert Braems, BART MATTHYS, Veronique Cocquyt, Hannelore Denys, Patrick Pauwels, and Louis Libbrecht. 2011. “Relationship Between Pathological Features, HER2 Protein Expression and HER2 and CEP17 Copy Number in Breast Cancer: Biological and Methodological Considerations.” Journal of Clinical Pathology 64 (3): 200–207.
APA
Lambein, Kathleen, Praet, M., Forsyth, R., Van den Broecke, R., Braems, G., MATTHYS, B., Cocquyt, V., et al. (2011). Relationship between pathological features, HER2 protein expression and HER2 and CEP17 copy number in breast cancer: biological and methodological considerations. JOURNAL OF CLINICAL PATHOLOGY, 64(3), 200–207.
Vancouver
1.
Lambein K, Praet M, Forsyth R, Van den Broecke R, Braems G, MATTHYS B, et al. Relationship between pathological features, HER2 protein expression and HER2 and CEP17 copy number in breast cancer: biological and methodological considerations. JOURNAL OF CLINICAL PATHOLOGY. 2011;64(3):200–7.
MLA
Lambein, Kathleen, Marleen Praet, Ramses Forsyth, et al. “Relationship Between Pathological Features, HER2 Protein Expression and HER2 and CEP17 Copy Number in Breast Cancer: Biological and Methodological Considerations.” JOURNAL OF CLINICAL PATHOLOGY 64.3 (2011): 200–207. Print.