Putative Clinical Potential of <i>ERBB2</i> Amplification Assessment by ddPCR in FFPE-DNA and cfDNA of Gastroesophageal Adenocarcinoma Patients
Anti-HER2 monoclonal antibody trastuzumab improves the survival of those patients with advanced gastroesophageal adenocarcinoma (GEA) exhibiting HER2/<i>ERBB2</i> overexpression/amplification. The current gold standard methods used to diagnose the HER2 status in GEA are immunohistochemis...
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MDPI AG
2022-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/9/2180 |
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| author | Elisa Boldrin Marcodomenico Mazza Maria Assunta Piano Rita Alfieri Isabella Monia Montagner Giovanna Magni Maria Chiara Scaini Loretta Vassallo Antonio Rosato Pierluigi Pilati Antonio Scapinello Matteo Curtarello |
| author_facet | Elisa Boldrin Marcodomenico Mazza Maria Assunta Piano Rita Alfieri Isabella Monia Montagner Giovanna Magni Maria Chiara Scaini Loretta Vassallo Antonio Rosato Pierluigi Pilati Antonio Scapinello Matteo Curtarello |
| author_sort | Elisa Boldrin |
| collection | DOAJ |
| description | Anti-HER2 monoclonal antibody trastuzumab improves the survival of those patients with advanced gastroesophageal adenocarcinoma (GEA) exhibiting HER2/<i>ERBB2</i> overexpression/amplification. The current gold standard methods used to diagnose the HER2 status in GEA are immunohistochemistry (IHC) and silver or fluorescence in situ hybridization (SISH or FISH). However, they do not permit spatial and temporal tumor monitoring, nor do they overcome intra-cancer heterogeneity. Droplet digital PCR (ddPCR) was used to implement the assessment of HER2 status in formalin-fixed paraffin-embedded (FFPE) tumor DNA from a retrospective cohort (86 patients) and in cell-free DNA (cfDNA) samples from a prospective cohort (28 patients). In comparison to IHC/SISH, ddPCR assay revealed <i>ERBB2</i> amplification in a larger patient fraction, including HER2 2+ and 0–1+ of the retrospective cohort (45.3% vs. 15.1%). In addition, a considerable number of HER2 2+ and 0–1+ prospective patients who were negative in FFPE by both IHC/SISH and ddPCR, showed <i>ERBB2</i> amplification in the cfDNA collected just before surgery. cfDNA analysis in a few longitudinal cases revealed an increasing <i>ERBB2</i> trend at progression. In conclusion, ddPCR in liquid biopsy may improve the detection rate of HER2 positive patients, preventing those patients who could benefit from targeted therapy from being incorrectly excluded. |
| first_indexed | 2024-03-10T04:18:26Z |
| format | Article |
| id | doaj.art-e3ec3f3f70f84c7da93300e8f650af99 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T04:18:26Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-e3ec3f3f70f84c7da93300e8f650af992023-11-23T07:55:59ZengMDPI AGCancers2072-66942022-04-01149218010.3390/cancers14092180Putative Clinical Potential of <i>ERBB2</i> Amplification Assessment by ddPCR in FFPE-DNA and cfDNA of Gastroesophageal Adenocarcinoma PatientsElisa Boldrin0Marcodomenico Mazza1Maria Assunta Piano2Rita Alfieri3Isabella Monia Montagner4Giovanna Magni5Maria Chiara Scaini6Loretta Vassallo7Antonio Rosato8Pierluigi Pilati9Antonio Scapinello10Matteo Curtarello11Immunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padova, ItalySurgical Oncology of the Esophagus and Digestive Tract Unit, Veneto Institute of Oncology IOV-IRCCS, Via dei Carpani 16, 31033 Castelfranco Veneto, ItalyImmunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padova, ItalySurgical Oncology of the Esophagus and Digestive Tract Unit, Veneto Institute of Oncology IOV-IRCCS, Via dei Carpani 16, 31033 Castelfranco Veneto, ItalyPathology Unit, Veneto Institute of Oncology IOV-IRCCS, Via dei Carpani 16, 31033 Castelfranco Veneto, ItalyClinical Research Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padova, ItalyImmunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padova, ItalyPathology Unit, Veneto Institute of Oncology IOV-IRCCS, Via dei Carpani 16, 31033 Castelfranco Veneto, ItalyImmunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padova, ItalySurgical Oncology of the Esophagus and Digestive Tract Unit, Veneto Institute of Oncology IOV-IRCCS, Via dei Carpani 16, 31033 Castelfranco Veneto, ItalyPathology Unit, Veneto Institute of Oncology IOV-IRCCS, Via dei Carpani 16, 31033 Castelfranco Veneto, ItalyImmunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padova, ItalyAnti-HER2 monoclonal antibody trastuzumab improves the survival of those patients with advanced gastroesophageal adenocarcinoma (GEA) exhibiting HER2/<i>ERBB2</i> overexpression/amplification. The current gold standard methods used to diagnose the HER2 status in GEA are immunohistochemistry (IHC) and silver or fluorescence in situ hybridization (SISH or FISH). However, they do not permit spatial and temporal tumor monitoring, nor do they overcome intra-cancer heterogeneity. Droplet digital PCR (ddPCR) was used to implement the assessment of HER2 status in formalin-fixed paraffin-embedded (FFPE) tumor DNA from a retrospective cohort (86 patients) and in cell-free DNA (cfDNA) samples from a prospective cohort (28 patients). In comparison to IHC/SISH, ddPCR assay revealed <i>ERBB2</i> amplification in a larger patient fraction, including HER2 2+ and 0–1+ of the retrospective cohort (45.3% vs. 15.1%). In addition, a considerable number of HER2 2+ and 0–1+ prospective patients who were negative in FFPE by both IHC/SISH and ddPCR, showed <i>ERBB2</i> amplification in the cfDNA collected just before surgery. cfDNA analysis in a few longitudinal cases revealed an increasing <i>ERBB2</i> trend at progression. In conclusion, ddPCR in liquid biopsy may improve the detection rate of HER2 positive patients, preventing those patients who could benefit from targeted therapy from being incorrectly excluded.https://www.mdpi.com/2072-6694/14/9/2180liquid biopsycell-free DNA (cfDNA)HER2<i>ERBB2</i>gastroesophageal adenocarcinomadroplet digital PCR (ddPCR) |
| spellingShingle | Elisa Boldrin Marcodomenico Mazza Maria Assunta Piano Rita Alfieri Isabella Monia Montagner Giovanna Magni Maria Chiara Scaini Loretta Vassallo Antonio Rosato Pierluigi Pilati Antonio Scapinello Matteo Curtarello Putative Clinical Potential of <i>ERBB2</i> Amplification Assessment by ddPCR in FFPE-DNA and cfDNA of Gastroesophageal Adenocarcinoma Patients Cancers liquid biopsy cell-free DNA (cfDNA) HER2 <i>ERBB2</i> gastroesophageal adenocarcinoma droplet digital PCR (ddPCR) |
| title | Putative Clinical Potential of <i>ERBB2</i> Amplification Assessment by ddPCR in FFPE-DNA and cfDNA of Gastroesophageal Adenocarcinoma Patients |
| title_full | Putative Clinical Potential of <i>ERBB2</i> Amplification Assessment by ddPCR in FFPE-DNA and cfDNA of Gastroesophageal Adenocarcinoma Patients |
| title_fullStr | Putative Clinical Potential of <i>ERBB2</i> Amplification Assessment by ddPCR in FFPE-DNA and cfDNA of Gastroesophageal Adenocarcinoma Patients |
| title_full_unstemmed | Putative Clinical Potential of <i>ERBB2</i> Amplification Assessment by ddPCR in FFPE-DNA and cfDNA of Gastroesophageal Adenocarcinoma Patients |
| title_short | Putative Clinical Potential of <i>ERBB2</i> Amplification Assessment by ddPCR in FFPE-DNA and cfDNA of Gastroesophageal Adenocarcinoma Patients |
| title_sort | putative clinical potential of i erbb2 i amplification assessment by ddpcr in ffpe dna and cfdna of gastroesophageal adenocarcinoma patients |
| topic | liquid biopsy cell-free DNA (cfDNA) HER2 <i>ERBB2</i> gastroesophageal adenocarcinoma droplet digital PCR (ddPCR) |
| url | https://www.mdpi.com/2072-6694/14/9/2180 |
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