PMID- 23634290 OWN - NLM STAT- MEDLINE DCOM- 20140207 LR - 20211021 IS - 2045-7634 (Print) IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 2 IP - 2 DP - 2013 Apr TI - Discordance in HER2 gene amplification in circulating and disseminated tumor cells in patients with operable breast cancer. PG - 226-33 LID - 10.1002/cam4.70 [doi] AB - Human epidermal growth factor receptor 2 (HER2) gene amplification in circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) might be useful for modifying Herceptin therapy in breast cancer. In the process of investigating the utility of a microfluidic platform for detecting HER2 gene amplification in these cells, we observed novel results on discordance of HER2 status. Peripheral blood (8.5 mL) and bone marrow (BM) (7.5-10 mL) were collected prospectively from patients with clinical stages I-IV breast cancer. Mononuclear cells were recovered, stained with cytokeratin (CK), CD45, and DAPI, and processed through microfluidic channels for fluorescence in situ hybridization (FISH). A ratio of HER2:CEP17 >2 in any CK+/CD45 or CK-/CD45 cell was regarded as positive for HER2 gene amplification. Peripheral blood from 95 patients and BM from 78 patients were studied. We found CK+/CD45-/DAPI+ CTCs in 27.3% of patients. We evaluated HER2 gene amplification by FISH in 88 blood and 78 BM specimens and found HER2+ CTCs in 1 of 9 (11.1%) and HER2+ DTCs (27.2%) in 3 of 11 patients with HER2+ primary tumor. Among patients with a HER2- primary tumor, 5 of 79 had HER2+ CTCs (6.3%) and 14 of 67 had HER2+ DTCs (20.8%). The overall rate of discordance in HER2 status was 15% between primary tumor and CTCs and 28.2% between primary tumor and DTCs. HER2 was amplified in CTCs and DTCs in a portion of both HER2+ and HER2- primary tumors. HER2 discordance was more frequent for DTCs. The clinical implications of evaluating HER2 status in CTCs and DTCs in breast cancer needs to be established in prospective clinical trials. The cell enrichment and extraction microfluidic technology provides a sensitive platform for evaluation of HER2 gene amplification in CTCs and DTCs. FAU - Krishnamurthy, Savitri AU - Krishnamurthy S AD - Department of Pathology, The University of Texas MD Anderson Cancer Center Houston, Texas 77030, USA. skrishna@mdanderson.org FAU - Bischoff, Farideh AU - Bischoff F FAU - Ann Mayer, Julie AU - Ann Mayer J FAU - Wong, Karina AU - Wong K FAU - Pham, Tam AU - Pham T FAU - Kuerer, Henry AU - Kuerer H FAU - Lodhi, Ashutosh AU - Lodhi A FAU - Bhattacharyya, Anirban AU - Bhattacharyya A FAU - Hall, Carolyn AU - Hall C FAU - Lucci, Anthony AU - Lucci A LA - eng GR - DAMD 17-03-01-0669/PHS HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20130306 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 RN - 0 (Biomarkers, Tumor) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Biomarkers, Tumor/genetics MH - Breast Neoplasms/*genetics/surgery MH - Female MH - *Gene Amplification MH - Humans MH - In Situ Hybridization, Fluorescence MH - Neoplastic Cells, Circulating/*metabolism MH - Receptor, ErbB-2/*genetics MH - Tumor Cells, Cultured PMC - PMC3639661 OTO - NOTNLM OT - Breast cancer OT - HER2 status OT - circulating tumor cells OT - disseminated tumor cells OT - minimal residual disease EDAT- 2013/05/02 06:00 MHDA- 2013/05/02 06:01 PMCR- 2013/04/01 CRDT- 2013/05/02 06:00 PHST- 2012/07/15 00:00 [received] PHST- 2013/01/25 00:00 [revised] PHST- 2013/01/28 00:00 [accepted] PHST- 2013/05/02 06:00 [entrez] PHST- 2013/05/02 06:00 [pubmed] PHST- 2013/05/02 06:01 [medline] PHST- 2013/04/01 00:00 [pmc-release] AID - 10.1002/cam4.70 [doi] PST - ppublish SO - Cancer Med. 2013 Apr;2(2):226-33. doi: 10.1002/cam4.70. Epub 2013 Mar 6.