Department of Gastroenterology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
PLoS One. 2022 Jul 25;17(7):e0270591. doi: 10.1371/journal.pone.0270591. eCollection 2022.
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.
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.
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).
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.
接受霍奇金淋巴瘤（HL）或睾丸癌（TC）放疗的患者发生胃癌的风险增加。本研究旨在评估 HL/TC 治疗后发生的胃腺癌（t-GC）是否在分子上与普通人群中的胃腺癌不同。
患者在 HL/TC 治疗后≥5 年被诊断为 t-GC。使用免疫组织化学和分子分析方法鉴定了 4 种分子亚型：EB 病毒（EBV）、错配修复（MMR）缺陷或微卫星不稳定（MSI）、异常的 p53 染色作为染色体不稳定性（sCIN）的替代物，以及没有这些异常的基因组稳定性的替代物（sGS）。结果与文献中描述的普通人群中的胃癌（p-GC）进行了比较。
对 90 例 t-GC 进行分子亚型分析，结果显示 3%为 EBV 型、8%为 MSI 型、36%为 sCIN 型和 53%为 sGS 型。6 例 MSI t-GC 中有 3 例 MLH1 启动子甲基化，2 例解释为 MMR 基因的双体细胞突变。与 p-GC 相比，t-GC 更常为 sGS 型（53% vs. 38%，p = 0.04）。1990 年前诊断的 HL/TC 患者的 t-GC 比 1990 年后更常为 sGS 型（63% vs. 38%，p = 0.03）。位于接受高放射剂量的胃窦区的 t-GC 更常为 sGS 型（与 p-GC 相比，61% vs. 28%，p = 0.02）。
我们的研究结果表明，与 p-GC 相比，t-GC 更常为 sGS 型。HL/TC 患者在 1990 年前接受过抗癌治疗，治疗范围更广，因此 t-GC 的 sGS 亚型与既往抗癌治疗有关。
