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Putative Clinical Potential of ERBB2 Amplification Assessment by ddPCR in FFPE-DNA and cfDNA of Gastroesophageal Adenocarcinoma Patients

SIMPLE SUMMARY: Gastroesophageal adenocarcinoma (GEA) has a poor prognosis. However, since the HER2 positive subgroup could benefit from trastuzumab targeted therapy, considerable effort has been spent in determining the HER2 status in these patients. To date, immunohistochemistry and in situ hybrid...

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Detalles Bibliográficos
Autores principales: Boldrin, Elisa, Mazza, Marcodomenico, Piano, Maria Assunta, Alfieri, Rita, Montagner, Isabella Monia, Magni, Giovanna, Scaini, Maria Chiara, Vassallo, Loretta, Rosato, Antonio, Pilati, Pierluigi, Scapinello, Antonio, Curtarello, Matteo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102116/
https://www.ncbi.nlm.nih.gov/pubmed/35565309
http://dx.doi.org/10.3390/cancers14092180
Descripción
Sumario:SIMPLE SUMMARY: Gastroesophageal adenocarcinoma (GEA) has a poor prognosis. However, since the HER2 positive subgroup could benefit from trastuzumab targeted therapy, considerable effort has been spent in determining the HER2 status in these patients. To date, immunohistochemistry and in situ hybridization are the gold standard methods for assessing HER2/ERBB2 overexpression/amplification in tumor specimens. However, they have several limitations due to their cost, the large number of undetermined cases, and the impossibility of longitudinal patient monitoring. Here, we report the potential of a molecular method (droplet digital PCR) to investigate ERBB2 status in both solid and liquid biopsies of GEA. Results suggest that this methodology could be used to implement current histological analysis in solid biopsy and that it may be feasible in liquid biopsy. An alternative, more sensitive method of assessing HER2 status may aid physicians in their therapeutic decision-making, benefiting the patient. Liquid biopsy could also overcome the limitations of tissue-based analyses. ABSTRACT: 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.