Department of Anatomic Pathology, Pontificia Universidad Católica de Chile, Santiago, Chile.
Clin Cancer Res. 2010 Jun 15;16(12):3253-9. doi: 10.1158/1078-0432.CCR-09-2491. Epub 2010 Jun 8.
Histologic assessment of high-risk gastritis for the development of gastric cancer is not well defined. The identification of tissue markers together with the integration of histologic features will be required for this assessment.
Matched tumor/nontumor adjacent mucosa (NTAM) of 91 early gastric cancer and 148 chronic gastritis cases were evaluated for histologic characteristics (atrophy, intestinal metaplasia, chronic inflammation, polymorphonuclear infiltration, and Helicobacter pylori) by the Sydney System. Atrophy risk assessment was also evaluated by the Operative Link on Gastritis Assessment (OLGA) staging system. Eight tissue markers (BRCA1, HSP90, STAT1, FHIT, EGFR, p73, p53, p16INK4a) and EBV were also evaluated by tissue microarray/immunohistochemistry/in situ hybridization platform. Data were analyzed by contingency tables (2 x 2) using Fisher's exact two-tailed test (P < 0.001) and integrated by Significance Analysis of Microarrays (SAM) and clustering analysis.
Histologically, NTAM have severe intestinal metaplasia/chronic inflammation and severe atrophy assessed by Sydney and OLGA staging systems. H. pylori infection was similar in both groups, and EBV was found only in 5.5% of the tumor samples. Overexpression of p73 was higher in NTAM (50.5%) than in chronic gastritis (10.8%; P < 0.0001). Integration of histologic features and tissue markers showed that overexpression of p73, severe atrophy, and OLGA stage 4 were the most relevant features in NTAM. Clustering analysis correctly assigned NTAM and control cases (P < 0.0001).
Overexpression of p73 should be considered for the assessment of high-risk chronic gastritis. SAM allows the integration of histology and tissue markers for this assessment.
对于胃癌发展的高危性胃炎的组织学评估尚不完善。需要识别组织标志物，并将组织学特征整合在一起，以进行这种评估。
对 91 例早期胃癌和 148 例慢性胃炎患者的肿瘤/非肿瘤相邻黏膜（NTAM）进行组织学特征（萎缩、肠化生、慢性炎症、多形核浸润和幽门螺杆菌）评估，采用悉尼系统。萎缩风险评估也采用操作链接胃炎评估（OLGA）分期系统进行。还通过组织微阵列/免疫组织化学/原位杂交平台评估了 8 种组织标志物（BRCA1、HSP90、STAT1、FHIT、EGFR、p73、p53、p16INK4a）和 EBV。通过使用 Fisher 的精确二项式检验（P < 0.001）对 2x2 列联表进行数据分析，并通过 Significance Analysis of Microarrays（SAM）和聚类分析进行整合。
组织学上，NTAM 具有严重的肠化生/慢性炎症和悉尼和 OLGA 分期系统评估的严重萎缩。两组的幽门螺杆菌感染相似，只有 5.5%的肿瘤样本中发现 EBV。p73 的过表达在 NTAM（50.5%）中高于慢性胃炎（10.8%；P < 0.0001）。组织学特征和组织标志物的整合表明，p73 的过表达、严重萎缩和 OLGA 第 4 期是 NTAM 中最相关的特征。聚类分析正确地分配了 NTAM 和对照病例（P < 0.0001）。
p73 的过表达应考虑用于高危性慢性胃炎的评估。SAM 允许对这种评估进行组织学和组织标志物的整合。
