Hoffmann, Martin and Pasch, Sophie and Schamberger, Thomas and Maneck, Matthias and Moehlendick, Birte and Schumacher, Sarah and Brockhoff, Gero and Knoefel, Wolfram Trudo and Izbicki, Jakob and Polzer, Bernhard and Stoecklein, Nikolas H. and Klein, Christoph A. (2018) Diagnostic pathology of early systemic cancer: ERBB2 gene amplification in single disseminated cancer cells determines patient survival in operable esophageal cancer. INTERNATIONAL JOURNAL OF CANCER, 142 (4). pp. 833-843. ISSN 0020-7136, 1097-0215
Full text not available from this repository. (Request a copy)Abstract
Early metastatic dissemination and evolution of disseminated cancer cells (DCCs) outside the primary tumor is one reason for the failure of adjuvant therapies because it generates molecular genotypes and phenotypes different from primary tumors, which still underlie therapy decisions. Since ERBB2 amplification in esophageal DCCs but not in primary tumor cells predict outcome, we aimed to establish an assay with diagnostic reliability for single DCCs or circulating tumor cells. For this, we evaluated copy number alterations of more than 600 single DCCs from multiple cancer types to define reference regions suitable for quantification of target regions, such as ERBB2. We then compared ERBB2 quantitative PCR (qPCR) measurements with fluorescent in situ hybridization (FISH) data of various breast cancer cell lines and identified the aberration-calling threshold. The method was applied to two independent cohorts of esophageal cancer patients from Hamburg (n = 59) and Dusseldorf (n = 53). We found a high correlation between the single cell qPCR assay and the standard FISH assay (R = 0.98) and significant associations between amplification and survival for both patient cohorts (Hamburg (HH), p = 0.033; Dusseldorf (D), p = 0.052; pooled HH+D, p = 0.002) when applied to DCCs of esophageal cancer patients. Detection of a single ERBB2-amplified DCC was the most important risk factor for death from esophageal cancer (relative risk = 4.22; 95% CI = 1.91-9.32; p<0.001). In our study, we detected ERBB2-amplified cells in 7% of patients. These patients could benefit from anti-ERBB2 targeting therapies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CIRCULATING TUMOR-CELLS; COMPARATIVE GENOMIC HYBRIDIZATION; METASTATIC BREAST-CANCER; ESOPHAGOGASTRIC CANCER; MICROMETASTATIC CELLS; PROGNOSTIC IMPACT; MELANOMA-CELLS; BONE-MARROW; HER2 STATUS; ADENOCARCINOMA; metastasis; single disseminated cancer cells; esophageal cancer; ERBB2 gene amplification; quantitative PCR |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für experimentelle Medizin und Therapieverfahren |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Mar 2020 09:15 |
| Last Modified: | 18 Mar 2020 09:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15043 |
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