Maspin 差异表达模式作为食管腺癌/胃食管结合部腺癌靶向筛查的潜在标志物。

Maspin differential expression patterns as a potential marker for targeted screening of esophageal adenocarcinoma/gastroesophageal junction adenocarcinoma.

机构信息

Department of Oncology, Wayne State University School of Medicine, Detroit, United States of America.

Department of Pathology, Wayne State University School of Medicine, Detroit, United States of America.

出版信息

PLoS One. 2019 Apr 19;14(4):e0215089. doi: 10.1371/journal.pone.0215089. eCollection 2019.

Abstract

AIM

Barrett's esophagus (BE) is a predisposing factor of esophageal adenocarcinoma/gastroesophageal junction adenocarcinoma (ECA/GEJ Aca). BE patients are stratified and subsequently monitored according to the risk of malignant progression by the combination of endoscopy and biopsy. This study is to evaluate the maspin expression patterns as early diagnostic markers of malignancy in BE patients.

MATERIALS AND METHODS

Immunohistochemistry (IHC) staining was performed on 62 archival core biopsies from 35 patients, including BE without dysplasia (intestinal metaplasia, IM), BE with low grade dysplasia, BE with high grade dysplasia, carcinoma in situ, and well to poorly differentiated ECA/GEJ Aca (PD-ECA/GEJ Aca). The intensity and the subcellular distribution of immunoreactivity were evaluated microscopically. Statistical analysis was performed using the χ2 and Fisher exact tests.

RESULTS

The level of epithelial-specific tumor suppressor maspin protein inversely correlated with the progression from IM to PD-ECA/GEJ Aca. Lesions of each pathological grade could be divided into subtypes that exhibited distinct maspin subcellular distribution patterns, including nuclear only (Nuc), combined nuclear and cytoplasmic (Nuc+Cyt), cytoplasmic only (Cyt) and overall negligible (Neg). The Cyt subtype, which was minor in both IM and dysplasia (approximately 10%), was predominant in ECA/GEJ Aca as early as well-differentiated lesions (more than 50%: p = 0.0092). In comparison, nuclear staining of the tumor suppressor TP53 was heterogeneous in dysplasia, and did not correlate with the differentiation grades of ECA/GEJ Aca.

CONCLUSION

The Cyt subtype of maspin expression pattern in core biopsies of BE patients may serve as a molecular marker for early diagnosis of ECA/GEJ Aca.

摘要

目的

巴雷特食管(BE)是食管腺癌/胃食管交界处腺癌(ECA/GEJ Aca)的一个诱发因素。BE 患者根据内镜和活检的恶性进展风险进行分层,并随后进行监测。本研究旨在评估 maspin 表达模式作为 BE 患者恶性肿瘤的早期诊断标志物。

材料和方法

对 35 名患者的 62 份存档核心活检进行免疫组织化学(IHC)染色,包括无异型增生的 BE(肠上皮化生,IM)、低级别异型增生的 BE、高级别异型增生的 BE、原位癌和从高分化到低分化的 ECA/GEJ Aca(PD-ECA/GEJ Aca)。显微镜下评估免疫反应的强度和亚细胞分布。使用 χ2 和 Fisher 精确检验进行统计分析。

结果

上皮特异性肿瘤抑制因子 maspin 蛋白的水平与从 IM 到 PD-ECA/GEJ Aca 的进展呈负相关。每个病理分级的病变可分为表现出不同 maspin 亚细胞分布模式的亚型,包括仅核(Nuc)、核质共表达(Nuc+Cyt)、仅细胞质(Cyt)和整体可忽略不计(Neg)。在 IM 和异型增生中,Cyt 亚型(约 10%)较少,在 ECA/GEJ Aca 中,即使是低分化病变,也以主要的 Cyt 亚型为主(超过 50%:p=0.0092)。相比之下,肿瘤抑制因子 TP53 的核染色在异型增生中呈异质性,与 ECA/GEJ Aca 的分化等级无关。

结论

BE 患者核心活检中 maspin 表达模式的 Cyt 亚型可能作为 ECA/GEJ Aca 的早期诊断分子标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd6/6474598/9f5969faa19f/pone.0215089.g001.jpg

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