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基于新型分子生物标志物的胃癌免疫组织化学分类:一种潜在的生存预测指标。

Immunohistochemical classification of gastric cancer based on new molecular biomarkers: a potential predictor of survival.

机构信息

Department of Surgical Pathology, Hospital Clínico San Carlos, 28040, Madrid, Spain.

Complutense University of Madrid, Madrid, Spain.

出版信息

Virchows Arch. 2018 Dec;473(6):687-695. doi: 10.1007/s00428-018-2443-9. Epub 2018 Aug 23.

Abstract

Several classification systems have been described for stratifying patients with gastric carcinoma (GC). However, their prognostic value is low, and there is an urgent need for identification of molecular markers and development of new classifications. Retrospective study of 206 cases of GC diagnosed and surgically resected in our hospital between 2000 and 2017. Clinicopathological features of all cases were assessed and tissue microarrays were constructed for immunohistochemical (IHC) study. Patients were stratified based on IHC results. Mean patient age was 71 years and most patients were male (54.6%). Most tumors were located in the gastric antrum and body, and they were mostly fungoid or ulcerative lesions. GC were mainly intestinal-type tumors and 60.3% were diagnosed at pT3. 56.2% of patients showed recurrences and 29.4% died due to GC. According to our IHC classification, 23.5% of tumors showed microsatellite instability, 6% were E-cadherin negative, 53.5% were stable-p53 not overexpressed, and 17% were stable with p53 overexpression. IHC classification was significantly correlated with patient gender, gross morphology, Laurén classification, tumor necrosis, perineural infiltration, type of leading edge, and patient outcome. Multivariate analysis showed that IHC subtype was significantly and independently associated with overall survival, together with clinical symptoms, signet cell phenotype, tumor grade and vessel invasion. The application of IHC classifications based on molecular biomarkers in clinical practice can aid in the stratification of GC patients. More studies are needed to evaluate the reproducibility and clinical significance of these classifications.

摘要

几种用于分层胃腺癌 (GC) 患者的分类系统已经被描述。然而,它们的预后价值较低,迫切需要识别分子标志物和开发新的分类。回顾性研究了 206 例 2000 年至 2017 年在我院诊断和手术切除的 GC 病例。评估了所有病例的临床病理特征,并构建组织微阵列进行免疫组织化学 (IHC) 研究。根据 IHC 结果对患者进行分层。患者平均年龄为 71 岁,大多数为男性 (54.6%)。大多数肿瘤位于胃窦和体部,多为蕈伞型或溃疡型病变。GC 主要为肠型肿瘤,60.3%诊断为 pT3。56.2%的患者出现复发,29.4%死于 GC。根据我们的 IHC 分类,23.5%的肿瘤表现出微卫星不稳定,6%的肿瘤 E-钙黏蛋白阴性,53.5%的肿瘤 p53 稳定且不表达过度,17%的肿瘤 p53 稳定且表达过度。IHC 分类与患者性别、大体形态、Laurén 分类、肿瘤坏死、神经周围浸润、前沿类型和患者预后显著相关。多变量分析显示,IHC 亚型与总生存显著相关,且与临床症状、印戒细胞表型、肿瘤分级和血管浸润独立相关。基于分子标志物的 IHC 分类在临床实践中的应用有助于分层 GC 患者。需要更多的研究来评估这些分类的重现性和临床意义。

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