Absence of chromosome 17 polysomy in breast cancer: analysis by CEP17 chromogenic in situ hybridization and multiplex ligation-dependent probe amplification
- PMID: 19760503
- DOI: 10.1007/s10549-009-0539-2
Absence of chromosome 17 polysomy in breast cancer: analysis by CEP17 chromogenic in situ hybridization and multiplex ligation-dependent probe amplification
Abstract
Amplification of the HER2 gene, present in 15-30% of breast carcinomas, correlates with poor outcome and is an indication for treatment with trastuzumab. Standard testing methods for HER2 amplification are fluorescence (FISH) or chromogenic in situ hybridization (CISH). In FISH/CISH scoring, correction for chromosome 17 polysomy is believed to be critical for determination of true HER2 amplification as opposed to increased chromosome 17 copy number. The term "polysomy 17" is widely used and defined as > or =3 copies of the chromosome 17 centromere (probe CEP17, D17Z1). Thus, the centromere is assumed to be representative for the entire chromosome. This study aimed to investigate the frequency of polysomy 17 and its association with HER2 amplification in 111 invasive breast cancer patients by CEP17 CISH and by copy number analysis of a set of 17 genes along chromosome 17 using multiplex ligation-dependent probe amplification (MLPA).Chromosome 17 usually showed a complex pattern of gains and losses by MLPA, unrelated to the copy number status of the centromere. Increase in centromere 17 copy number (denoted "polysomy 17"), as assessed by CEP17 CISH, was found in 19% of the patients. Of these patients, 60% also showed amplification of HER2 measured by MLPA. However, none of the 111 patients showed a true polysomy of chromosome 17 by MLPA. Only two patients (1.8%) had a possible gain of 17q. Amplification of 17p was not found in any of the patients, although a possible loss of 17p was found in one patient. In conclusion, this extensive analysis of amplicons along chromosome 17 shows that true polysomy of chromosome 17, either of the whole chromosome or of the short or the long arm, is very rare in invasive breast cancer. Abnormal CEP17 copy numbers may therefore actually stem from high level gains or amplification of CEP17 regardless of copy number gains of the short and long arms of chromosome 17 and, at least in some cases, correction with CEP17 probes may provide misleading HER2 gene status assessment results.
Similar articles
-
Effect of high copy number of HER2 associated with polysomy 17 on HER2 protein expression in invasive breast carcinoma.Diagn Mol Pathol. 2009 Mar;18(1):30-3. doi: 10.1097/PDM.0b013e31817c1af8. Diagn Mol Pathol. 2009. PMID: 19214111
-
Determining true HER2 gene status in breast cancers with polysomy by using alternative chromosome 17 reference genes: implications for anti-HER2 targeted therapy.J Clin Oncol. 2011 Nov 1;29(31):4168-74. doi: 10.1200/JCO.2011.36.0107. Epub 2011 Sep 26. J Clin Oncol. 2011. PMID: 21947821
-
The effect of chromosome 17 polysomy on HER-2/neu status in breast cancer.J Clin Pathol. 2008 Mar;61(3):317-21. doi: 10.1136/jcp.2007.050336. Epub 2007 Aug 30. J Clin Pathol. 2008. PMID: 17761736
-
HER2 in situ hybridization in breast cancer: clinical implications of polysomy 17 and genetic heterogeneity.Mod Pathol. 2014 Jan;27(1):4-18. doi: 10.1038/modpathol.2013.103. Epub 2013 Jun 28. Mod Pathol. 2014. PMID: 23807776 Review.
-
[HER2 gene amplification assay: is CISH an alternative to FISH?].Ann Pathol. 2003 Dec;23(6):617-22. Ann Pathol. 2003. PMID: 15094603 Review. French.
Cited by
-
HER2 Low Breast Cancer: A New Subtype or a Trojan for Cytotoxic Drug Delivery?Int J Mol Sci. 2023 May 4;24(9):8206. doi: 10.3390/ijms24098206. Int J Mol Sci. 2023. PMID: 37175916 Free PMC article. Review.
-
Updates on breast biomarkers.Virchows Arch. 2022 Jan;480(1):163-176. doi: 10.1007/s00428-022-03267-x. Epub 2022 Jan 14. Virchows Arch. 2022. PMID: 35029776 Review.
-
Impact of chromosome 17 centromere copy number increase on patient survival and human epidermal growth factor receptor 2 expression in gastric adenocarcinoma.Oncol Lett. 2021 Feb;21(2):142. doi: 10.3892/ol.2020.12403. Epub 2020 Dec 21. Oncol Lett. 2021. PMID: 33552261 Free PMC article.
-
Clinicopathologic features of breast cancer reclassified as HER2-amplified by fluorescence in situ hybridization with alternative chromosome 17 probes.Ann Diagn Pathol. 2020 Oct;48:151576. doi: 10.1016/j.anndiagpath.2020.151576. Epub 2020 Aug 8. Ann Diagn Pathol. 2020. PMID: 32805517 Free PMC article.
-
Secreted breast tumor interstitial fluid microRNAs and their target genes are associated with triple-negative breast cancer, tumor grade, and immune infiltration.Breast Cancer Res. 2020 Jun 30;22(1):73. doi: 10.1186/s13058-020-01295-6. Breast Cancer Res. 2020. PMID: 32605588 Free PMC article.
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous