PMID- 23313108 OWN - NLM STAT- MEDLINE DCOM- 20130412 LR - 20161125 IS - 2210-7762 (Print) VI - 206 IP - 1-2 DP - 2013 Jan-Feb TI - Change in HER2 (ERBB2) gene status after taxane-based chemotherapy for breast cancer: polyploidization can lead to diagnostic pitfalls with potential impact for clinical management. PG - 37-41 LID - S2210-7762(12)00276-1 [pii] LID - 10.1016/j.cancergen.2012.12.001 [doi] AB - The status of the HER2 (ERBB2) gene in breast cancer is not static and may change among the primary tumor, lymph node metastases, and distant metastases. This status change can be a consequence of the natural evolution of the tumor or can be induced by therapy. The HER2 gene status is, in the majority of cases, established at the moment of diagnosis. After chemotherapy, monitoring HER2 status can be a challenge because of ploidy changes induced by drugs. The cytogeneticist or the pathologist can face real difficulties in distinguishing between a true HER2 amplification and HER2 copy number increase by polyploidization. We performed a HER2 genetic examination by fluorescence in situ hybridization (FISH) of invasive breast cancers before and after taxane treatment. The majority of patients (91%) were HER2-negative both at diagnosis and after treatment. Thirty of 344 patients (9%) whose tumors were initially HER2-negative were found by FISH to have supernumerary HER2 gene copies (up to 15 copies) after neoadjuvant chemotherapy. This HER2 copy increase could not be attributed to true gene amplifications and instead reflected polyploidization events, which presumably affected all chromosomes. Indeed, when we used other FISH probes, we found other gene copy numbers to parallel those of HER2. We recommend careful checking of invasive breast carcinomas by supplementary FISH probes if the copy number of the HER2 gene is >6. This procedure allows the discrimination of specific HER2 gene amplifications and global increases in ploidy. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Valent, Alexander AU - Valent A AD - Molecular Pathology, Department of Pathology and Medical Biology, and Histocytopathology, Translational Research, Institut Gustave Roussy, Villejuif, France. alexander.valent@igr.fr FAU - Penault-Llorca, Frederique AU - Penault-Llorca F FAU - Cayre, Anne AU - Cayre A FAU - Kroemer, Guido AU - Kroemer G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130110 PL - United States TA - Cancer Genet JT - Cancer genetics JID - 101539150 RN - 0 (Aneugens) RN - 0 (Bridged-Ring Compounds) RN - 0 (Taxoids) RN - 1605-68-1 (taxane) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Aneugens/administration & dosage/adverse effects MH - Antineoplastic Combined Chemotherapy Protocols/*adverse effects/therapeutic use MH - Breast Neoplasms/*diagnosis/drug therapy/genetics/pathology MH - Bridged-Ring Compounds/administration & dosage/adverse effects MH - Carcinoma/*diagnosis/drug therapy/genetics/pathology MH - Case-Control Studies MH - Disease Progression MH - Female MH - Gene Amplification/drug effects MH - Gene Dosage/*drug effects MH - Gene Expression Regulation, Neoplastic/drug effects MH - Genes, erbB-2/*drug effects MH - Humans MH - Neoadjuvant Therapy MH - Polyploidy MH - Prognosis MH - Receptor, ErbB-2/drug effects/genetics MH - Taxoids/administration & dosage/adverse effects EDAT- 2013/01/15 06:00 MHDA- 2013/04/13 06:00 CRDT- 2013/01/15 06:00 PHST- 2012/06/11 00:00 [received] PHST- 2012/10/29 00:00 [revised] PHST- 2012/12/03 00:00 [accepted] PHST- 2013/01/15 06:00 [entrez] PHST- 2013/01/15 06:00 [pubmed] PHST- 2013/04/13 06:00 [medline] AID - S2210-7762(12)00276-1 [pii] AID - 10.1016/j.cancergen.2012.12.001 [doi] PST - ppublish SO - Cancer Genet. 2013 Jan-Feb;206(1-2):37-41. doi: 10.1016/j.cancergen.2012.12.001. Epub 2013 Jan 10.