Gastro-oesophageal adenocarcinomas (GOAs) are a common cause of cancer mortality worldwide.
Nowadays, beyond histological classification, the management of GOAs depends on molecular
classification. The Cancer Genome Atlas consortium identified four different molecular
subtypes of GOAs potentially allowing to tailor the treatment strategies [
[1]
]. About 20% of patients show an overexpression or amplification of the Human Epidermal
Growth Factor Receptor-2 (HER2). These tumors are generally microsatellite stable
(MSS) and present chromosomal instability [
[1]
]. The anti-HER2 monoclonal antibody trastuzumab combined with platinum and fluoropyrimidine
chemotherapy is the standard first line regimen for these patients [
[2]
]. Microsatellite instable (MSI) and DNA mismatch repair deficient (dMMR) cancers are
a distinct subtype of GOAs with a prevalence of up to ∼20% and being more frequent
in early stage [
[3]
]. These tumors are often associated with a hypermutated phenotype resulting in extensive
formation of cancer-specific neoantigens triggering robust anti-cancer immune responses.
They benefit extensively from anti-PD-1 immune checkpoint blockade [
[2]
,
[4]
]. Here, we describe a rare case of acquisition of MSI and the concomitant loss of
HER2 positivity potentially due to selective therapeutic pressure in a metastatic
MSS GOA treated with platinum-based chemotherapy and trastuzumab.Keywords
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Article info
Publication history
Published online: December 26, 2022
Accepted:
November 25,
2022
Received:
October 19,
2022
Publication stage
In Press Corrected ProofFootnotes
All the authors listed above declare no conflict of interest and financial disclosure related for this work. No funding or grant has been obtained for this work.
Identification
Copyright
© 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
