Putative Clinical Potential of ERBB2 Amplification Assessment by ddPCR in FFPE-DNA and cfDNA of Gastroesophageal Adenocarcinoma Patients.
Elisa BoldrinMarcodomenico MazzaMaria Assunta PianoRita AlfieriIsabella Monia MontagnerGiovanna MagniMaria Chiara ScainiLoretta VassalloAntonio RosatoPierluigi PilatiAntonio ScapinelloMatteo CurtarelloPublished in: Cancers (2022)
Anti-HER2 monoclonal antibody trastuzumab improves the survival of those patients with advanced gastroesophageal adenocarcinoma (GEA) exhibiting HER2/ ERBB2 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 ERBB2 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 ERBB2 amplification in the cfDNA collected just before surgery. cfDNA analysis in a few longitudinal cases revealed an increasing ERBB2 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.
Keyphrases
- end stage renal disease
- ejection fraction
- newly diagnosed
- squamous cell carcinoma
- peritoneal dialysis
- cell proliferation
- nucleic acid
- gold nanoparticles
- young adults
- single molecule
- high throughput
- minimally invasive
- transcription factor
- circulating tumor
- cell free
- patient reported
- ultrasound guided
- free survival
- papillary thyroid