Clinicopathological characteristics of Epstein-Barr virus and microsatellite instability subtypes of early gastric neoplasms classified by the Japanese and the World Health Organization criteria.

Clinicopathological characteristics of Epstein-Barr virus and microsatellite instability subtypes of early gastric neoplasms classified by the Japanese and the World Health Organization criteria.
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DOI:
10.1002/cjp2.209
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发表时间:
2021-07
期刊:
The journal of pathology. Clinical research
影响因子:
--
通讯作者:
Okumura T
Okumura T
中科院分区:
其他
文献类型:
--
作者:
Tanabe H;Mizukami Y;Takei H;Tamamura N;Omura Y;Kobayashi Y;Murakami Y;Kunogi T;Sasaki T;Takahashi K;Ando K;Ueno N;Kashima S;Yuzawa S;Hasegawa K;Sumi Y;Tanino M;Fujiya M;Okumura T

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胃癌是一种异质性疾病,具有不同的表型、基因型和临床结局,包括对治疗和复发的敏感性。最近的医学进展使这种异质性疾病的分类成几组,并随之分析其临床病理特征。与EB病毒(EBV)相关的胃癌和微卫星不稳定肿瘤被认为是两种主要亚型,因为它们分别通过成熟的方法(如原位杂交和基于聚合酶链反应的分析)明确定义。然而,在胃肿瘤的组织学诊断的差异仍然是一个问题,并应进行国际协调,以提高我们对胃癌发生的理解。我们根据目前的世界卫生组织(WHO)标准重新评估了日本早期胃癌病例,并根据微卫星不稳定性(MSI)和EBV阳性将其分为基因组亚型,以确定胃癌发生中的初始遗传事件。我们医院共存档了113例日本早期胃癌(包括低级别和高级别异型增生),这些患者在5年内接受了内镜切除术治疗。根据WHO标准进行的组织学重新评估显示54例腺癌,分为6例EBV阳性(11.1%),7例MSI高(MSI-H,13.0%)和41例微卫星稳定病例(75.9%)。通过错配修复蛋白的免疫组织化学测定证实了MSI-H腺癌。1例MSI-H腺癌病例(1/7,14.3%)的肿瘤细胞中,程序性死亡配体1免疫染色两种抗体(E1L3N和SP263)呈阳性。克隆SP263的染色细胞比例高于E1L3N。在组织学上,EBV阳性癌是低分化的(83.8%),MSI-H癌常见于高至中等分化的腺癌(85.7%),表明EBV阳性亚型即使在早期病变时也呈现高级别形态。我们的研究表明,WHO标准是有用的细分日本早期胃癌,这种细分可能是有用的比较分析的前体病变和早期癌。
Gastric cancer is a heterogenous disease with different phenotypes, genotypes, and clinical outcomes, including sensitivity to treatments and prognoses. Recent medical advances have enabled the classification of this heterogenous disease into several groups and the consequent analysis of their clinicopathological characteristics. Gastric cancer associated with Epstein–Barr virus (EBV) and microsatellite‐unstable tumors are considered to be the two major subtypes as they are clearly defined by well‐established methodologies, such as in situ hybridization and polymerase chain reaction‐based analyses, respectively. However, discrepancies in the histological diagnosis of gastric neoplasms remain problematic, and international harmonization should be performed to improve our understanding of gastric carcinogenesis. We re‐evaluated Japanese cases of early gastric cancer according to the current World Health Organization (WHO) criteria and classified them into genomic subtypes based on microsatellite instability (MSI) and EBV positivity to determine the initial genetic events in gastric carcinogenesis. A total of 113 Japanese early gastric cancers (including low‐ and high‐grade dysplasias) treated with endoscopic resection over 5 years were archived in our hospital. A histological re‐evaluation according to the WHO criteria revealed 54 adenocarcinomas, which were divided into 6 EBV‐positive (11.1%), 7 MSI‐high (MSI‐H, 13.0%), and 41 microsatellite stable cases (75.9%). MSI‐H adenocarcinoma was confirmed by an immunohistochemistry assay of mismatch repair proteins. Programmed death‐ligand 1 immunostaining with two antibodies (E1L3N and SP263) was positive in tumor cells of one MSI‐H adenocarcinoma case (1/7, 14.3%). The proportion of stained cells was higher with clone SP263 than with E1L3N. Histologically, EBV‐positive carcinomas were poorly differentiated (83.8%), and MSI‐H cancers were frequent in well to moderately differentiated adenocarcinoma (85.7%), indicating that the EBV‐positive subtype presented with high‐grade morphology even when an early lesion. Our study indicates that the WHO criteria are useful for subdividing Japanese early gastric cancers, and this subdivision may be useful for comparative analysis of precursor lesions and early carcinoma.
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