Assessment of HER2 status in invasive breast cancers with increased centromere 17 copy number
- PMID: 26223814
- DOI: 10.1007/s10549-015-3522-0
Assessment of HER2 status in invasive breast cancers with increased centromere 17 copy number
Abstract
This study was designed to evaluate usefulness of additional fluorescence in situ hybridization (FISH) using other reference genes on chromosome 17 for assessment of HER2 status in invasive breast cancers with increased centromere 17 copy number, and to compare this approach with conventional methods based on the 2007 and 2013 ASCO/CAP guidelines. We performed FISH with probes for SMS, RARA, and TP53 on 253 breast cancers with centromeric probe CEP17 copy number ≥ 2.6 using tissue microarrays. If one or more gene had a mean copy number <2.6, the largest number for that gene(s) was chosen as an alternative to CEP17 copy number. Of the 243 cases in which re-grading was possible, only 2 had copy numbers ≥ 2.6 for RARA, SMS, and TP53. Of the 151 breast cancers which were considered HER2 non-amplified by the 2007 ASCO/CAP guidelines using the HER2:CEP17 ratio, 42 (27.8%) were re-graded as amplified and 33 (21.8%) as equivocal after FISH using additional reference genes. Of the 101 HER2-non-amplified cases by the 2013 ASCO/CAP guidelines, 2 (2.0%) were reclassified as amplified and 24 (23.8%) as equivocal. Of 46 equivocal cases, 35 (76.1%) were re-graded as amplified. After re-grading, HER2-amplified cases were significantly increased, and the concordance between HER2 FISH and HER2 immunohistochemistry decreased. And some pathologic features of the cases which were designated to have HER2 amplification after additional FISH were not compatible with those of HER2-amplified breast cancers. The use of additional reference genes has been suggested as an option for accurate assessment of HER2 status in breast cancers with increased CEP17 copy number. However, this has limitations in that it can cause over-grading of HER2 status in tumors that lose the new reference genes. Thus, at present, it seems that additional FISH using other reference gene such as SMS, RARA, and TP53 for the cases with increased CEP17 copy number is not suitable for daily practice.
Similar articles
-
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
-
Co-amplification of the HER2 gene and chromosome 17 centromere: a potential diagnostic pitfall in HER2 testing in breast cancer.Breast Cancer Res Treat. 2012 Apr;132(3):925-35. doi: 10.1007/s10549-011-1642-8. Epub 2011 Jun 23. Breast Cancer Res Treat. 2012. PMID: 21698407
-
Updated 2013 College of American Pathologists/American Society of Clinical Oncology (CAP/ASCO) guideline recommendations for human epidermal growth factor receptor 2 (HER2) fluorescent in situ hybridization (FISH) testing increase HER2 positive and HER2 equivocal breast cancer cases; retrospective study of HER2 FISH results of 836 invasive breast cancers.Breast Cancer Res Treat. 2016 Jun;157(3):405-11. doi: 10.1007/s10549-016-3824-x. Epub 2016 May 14. Breast Cancer Res Treat. 2016. PMID: 27180259
-
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.
-
Double-Equivocal HER2 Invasive Breast Carcinomas: Institutional Experience and Review of Literature.Arch Pathol Lab Med. 2018 Dec;142(12):1511-1516. doi: 10.5858/arpa.2017-0265-RA. Epub 2018 Mar 29. Arch Pathol Lab Med. 2018. PMID: 29595316 Review.
Cited by
-
Clinicopathological Features of Breast Cancer with Polysomy 17 and Its Response to Neoadjuvant Chemotherapy.Eur J Breast Health. 2021 Mar 31;17(2):128-136. doi: 10.4274/ejbh.galenos.2021.2021-2-9. eCollection 2021 Apr. Eur J Breast Health. 2021. PMID: 33870112 Free PMC article.
-
Scanning window analysis of non-coding regions within normal-tumor whole-genome sequence samples.Brief Bioinform. 2021 May 20;22(3):bbaa203. doi: 10.1093/bib/bbaa203. Brief Bioinform. 2021. PMID: 32940334 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.
-
Invasive Micropapillary Carcinoma with CEP17 Monosomy of the Bilateral Breast: A Rare Case Report and Review of the Literature.Onco Targets Ther. 2020 Jul 2;13:6425-6432. doi: 10.2147/OTT.S251934. eCollection 2020. Onco Targets Ther. 2020. PMID: 32753884 Free PMC article.
-
HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation.J Pathol Transl Med. 2020 Jan;54(1):34-44. doi: 10.4132/jptm.2019.11.03. Epub 2019 Nov 6. J Pathol Transl Med. 2020. PMID: 31693827 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous