Morphological, clinical and molecular characteristics in ARID1a‑deficient microsatellite‑stable oesophageal adenocarcinoma

Rehkaemper,Jan; Gebauer,Florian; Ulmer,Bastian; Schallenberg,Simon; Bork,Julian; Zander,Thomas; Buettner,Reinhard; Bruns,Christiane Josephine; Schroeder,Wolfgang; Quaas,Alexander

doi:10.3892/ol.2023.13840

Morphological, clinical and molecular characteristics in ARID1a‑deficient microsatellite‑stable oesophageal adenocarcinoma

Authors:
- Jan Rehkaemper
- Florian Gebauer
- Bastian Ulmer
- Simon Schallenberg
- Julian Bork
- Thomas Zander
- Reinhard Buettner
- Christiane Josephine Bruns
- Wolfgang Schroeder
- Alexander Quaas
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Affiliations: Institute of Pathology, Visceral and Cancer Surgery, University Hospital of Cologne, D‑50937 Cologne, Germany, Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, D‑50937 Cologne, Germany, Institute of Pathology, Visceral and Cancer Surgery, University Hospital of Cologne, D‑50937 Cologne, Germany, Institute of Pathology, University Hospital Berlin‑Charite, D‑10117 Berlin, Germany, Department of Internal Medicine I, University Hospital of Cologne, D‑50937 Cologne, Germany, Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, D‑50937 Cologne, Germany
Published online on: April 26, 2023 https://doi.org/10.3892/ol.2023.13840
Article Number: 254

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Abstract

Publications describe the relevance of the AT‑rich interactive domain‑containing protein 1A (ARID1a) mutation in gastric adenocarcinoma, which occurs predominantly in the microsatellite instable (MSI)‑ and Epstein‑Barr virus (EBV)‑associated subtypes. It is unclear whether potential therapeutic, prognostic or morphologic descriptions are not epiphenomena of MSI (or EBV). Since personalised therapeutics are largely lacking for oesophageal adenocarcinoma (EAC), clinical trials investigating the efficacy of these therapeutics specifically in this subgroup are useful. To the best of our knowledge, this was the first study analysing the relevant tumour subset of microsatellite‑stable (MSS) EAC with loss of function of ARID1a. A total of 875 patients with EAC and data from The Cancer Genome Atlas (TCGA) were analysed. Statistical analyses associating previously known molecular characteristics of the present tumour cohort, overall survival, morphological growth patterns and tumour heterogeneity issues were considered. Subsequently, 10% of EAC were ARID1a‑deficient, the majority of which were MSS (7.5%). There was no characteristic growth pattern. Approximately 60% of tumours were PD‑L1 positive to varying degrees. TP53 mutations occurred together with ARID1a defective EAC in the present cohort and in the TCGA collective. The extent of 7.5% MSS‑EAC with ARID1a loss was unaffected by neoadjuvant therapy. ARID1a loss was often detected to be homogeneous (92%). ARID1a loss is not an epiphenomenon of MSI in EAC. The high homogeneity of ARID1a loss tumour clones could be considered an argument for the effectiveness of potential therapeutics. Since the majority of genomic ARID1a alterations result in protein loss, immunohistochemistry is a useful screening technique, especially in the absence of morphological characteristics.

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