Abstract
Introduction The risk of developing gastric cancer is increased in patients treated with radiotherapy for Hodgkin lymphoma (HL) or testicular cancer (TC). This study aims to assess if gastric adenocarcinoma after treatment for HL/TC (t-GC) is molecularly different from gastric adenocarcinoma in the general population. Methods Patients were diagnosed with t-GC ≥5 years after treatment for HL/TC. Four molecular subtypes were identified using immunohistochemical and molecular analyses: Epstein-Barr virus (EBV), mismatch repair (MMR) deficiency or microsatellite instability (MSI), aberrant p53 staining as surrogate for chromosomal instability (sCIN), and a surrogate for genomic stability (sGS) without these aberrations. Results were compared with gastric cancer in the general population (p-GC) described in literature. Results Molecular subtyping of 90 t-GCs resulted in 3% EBV, 8% MSI, 36% sCIN and 53% sGS. 3/6 of MSI t-GCs had MLH1 promoter methylation and 2/6 were explained by double somatic mutations in MMR genes. T-GCs were more frequently sGS than p-GCs (53% vs. 38%, p = 0.04). T-GC was more frequently sGS in HL/TC patients diagnosed before 1990, than after 1990 (63% vs. 38%, p = 0.03). T-GCs located in the antrum, an area that receives high irradiation doses, were more frequently sGS (61% vs. 28% in p-GCs, p = 0.02). Conclusion Our results demonstrate that t-GCs are more frequently of the sGS subtype than p-GCs. An association of t-GC of the sGS subtype with prior anticancer treatment is suggested by the high frequency in HL/TC patients who were treated before 1990, a time period in which HL/ TC treatments were more extensive.
| Original language | English |
|---|---|
| Article number | e0270591 |
| Pages (from-to) | e0270591 |
| Journal | PLoS ONE |
| Volume | 17 |
| Issue number | 7 July |
| DOIs | |
| Publication status | Published - 25 Jul 2022 |
Bibliographical note
Funding Information:M.E. van Leerdam obtained funding from the Dutch Society of Gastroenterology and Hepatology (Maag Lever Darm Stichting (MLDS) funding project FP14-04). F.E. van Leeuwen obtained funding from the Koningin Wilhelmina Onderzoeksprogramma (KWO 2010 - 4720). The other authors declare that they have no competing interests. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to acknowledge the NKI-AVL Core Facility Molecular Pathology & Biobanking (CFMPB), especially Sten Cornelissen, for supplying NKI-AVL Biobank material and /or lab support. We would also like to thank Koen van de Vijver for insights into immunohistochemistical analyses, Mohamed Achahchah for technical assistance, and all participating laboratories for the distribution of the t-GC material. We would like to thank the members of the PALGA group: L. Arensman, J.D. Burggraaf, G. van Ingen, J.W.R. Meijer, S.L. Meijer, S.H. Sastrowijoto. Finally, we would like to thank Winand Dinjens and Peggy Atmodimedjo for performing the somatic MMR gene mutation analyses and Hein te Riele for the thorough review of the manuscript.
Publisher Copyright:
Copyright: © 2022 Rigter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Other keywords
- Adenocarcinoma/genetics
- Brain Neoplasms
- Colorectal Neoplasms
- Epstein-Barr Virus Infections
- Herpesvirus 4, Human/genetics
- Hodgkin Disease/genetics
- Humans
- Male
- Microsatellite Instability
- Neoplasms, Germ Cell and Embryonal
- Neoplastic Syndromes, Hereditary
- Stomach Neoplasms/pathology
- Testicular Neoplasms