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胃癌在自身免疫性胃炎:一个组织病理学和分子研究
Valentina Angerilli1, Alessandro Vanoli2, Giulia Celin1
1Department of Medicine, Surgical Pathology Unit, University of Padua, Padua, Italy.
概括
与自身免疫性胃炎相关的胃癌 (GC) 通常是早期诊断的,并表现出神经内分泌特征. 这些GC表现出更高的不匹配修复缺陷率和高瘤突变负担,表明不同的分子特征.
科学领域:
- 胃肠病学 胃肠病学
- 在瘤学瘤学.
- 病理学 病理学 病理学
背景情况:
- 自免疫性胃炎 (AIG) 与1型神经内分泌瘤的风险显著增加有关.
- 在AIG患者中胃腺癌 (GC) 的风险不太清楚.
- 在AIG的背景下描述GC对于了解疾病进展和管理至关重要.
研究的目的:
- 调查自身免疫性胃炎 (AIG) 患者出现的胃癌 (GC) 的临床病理和分子特征.
- 在AIG相关的GC中识别特定的基因型,分子变化和潜在的生物标志物.
主要方法:
- 来自意大利机构的26个AIG相关的GC标本的分析.
- 包括MUCs,CDX2,HER2,PD-L1,CLDN18,MMR蛋白,p53和EBER在内的各种标记物的免疫组织化学.
- 在19个案例中,下一代测序了523个与癌症相关的基因.
- 组织学和免疫组织化学特征的专家病理审查.
主要成果:
- 大多数与AIG相关的GC在早期被诊断出来 (pT1,52%) 并且位于体/骨中.
- 组织型包括腺癌 (77%),混合的神经内分泌和非神经内分泌瘤 (11%),以及具有神经内分泌成分的其他类型.
- 重要发现包括MMR缺乏 (27%),HER2阳性 (12%),CLDN18阳性 (23%) 和PD-L1阳性 (42%).
- 分子分析显示26%的微卫星不稳定性 (MSI) 和37%的高瘤突变负担 (TMB).
- 经常发生变化的基因包括TP53 (42%),RNF43 (37%),ERBB2 (37%),ARID1A (32%) 和PIK3CA (21%).
结论:
- 与AIG相关的GC经常在较低的阶段被诊断出来,通常是患有未被识别的严重AIG的患者.
- 这些瘤通常表现出神经内分泌分化和独特的分子形状,包括较高的MMR缺乏率和高TMB.
- 调查结果强调需要提高对AIG患者的GC的认识,并为AIG患者量身定制的诊断/治疗策略.
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