通过组织微阵列评估胃腺癌中的细胞外凋亡信号通路。

The extrinsic apoptotic signaling pathway in gastric adenocarcinomas assessed by tissue microarray.

机构信息

Departamento de Patologia, Universidade Federal de São Paulo, UNIFESP, SP, Brazil.

出版信息

Pathol Res Pract. 2011 Oct 15;207(10):613-7. doi: 10.1016/j.prp.2011.06.010.

DOI:10.1016/j.prp.2011.06.010

Abstract

The purpose of this investigation was to analyze the immunoexpression of FasL, Fas, FADD, cleaved caspase 8, and cleaved caspase 3 in gastric cancer. Formalin-fixed and paraffin-embedded gastric adenocarcinoma tissues from 87 patients, including adjacent normal tissues, were included on tissue microarray by immunohistochemistry. The tumor and the adjacent normal tissues were positive for FasL in 66.7% and 90.6%, for Fas in 52.8% and 52.4%, for FADD in 67.4% and 82.3%, for cleaved caspase 8 in 27.9% and 37.7%, and for cleaved caspase 3 in 33.7% and 8.3%, respectively. FasL and the FADD from tumor were statistically different in relation to the histological type. Cleaved caspase 8 was statistically different in relation to clinical stage (p=0.031). The FADD from normal tissue was statistically different in relation to age (p=0.039), sex (p=0.055), clinical stage (p=0.019), and Fas was different in relation to tumor size (p=0.012). In the tumor, we observed a correlation between FasL and Fas, FasL and FADD, and FasL and cleaved caspase 3. In the adjacent normal tissue, a correlation was observed between FasL and Fas, FasL and FADD. There was no association of another marker with sex, age, clinical stage, and survival. Our results suggest that these proteins mediate the early extrinsic apoptotic pathway in gastric cancer and adjacent normal mucosa. FasL protein binds to Fas protein and subsequently binds to death receptor FADD signaling activation of the extrinsic apoptotic pathway. In this phase, there was inhibition of caspase 8 and, consequently, decreased apoptosis.

摘要

本研究旨在分析 FasL、Fas、FADD、cleaved caspase 8 和 cleaved caspase 3 在胃癌中的免疫表达。通过免疫组化，将 87 例患者的福尔马林固定石蜡包埋胃腺癌组织（包括相邻正常组织）制成组织微阵列。肿瘤和相邻正常组织 FasL 的阳性率分别为 66.7%和 90.6%，Fas 为 52.8%和 52.4%，FADD 为 67.4%和 82.3%，cleaved caspase 8 为 27.9%和 37.7%，cleaved caspase 3 为 33.7%和 8.3%。肿瘤 FasL 和 FADD 与组织学类型有关，差异有统计学意义。cleaved caspase 8 与临床分期有关，差异有统计学意义（p=0.031）。正常组织 FADD 与年龄有关，差异有统计学意义（p=0.039），与性别有关，差异有统计学意义（p=0.055），与临床分期有关，差异有统计学意义（p=0.019），与 Fas 有关，差异有统计学意义（p=0.012）。在肿瘤中，我们观察到 FasL 与 Fas、FasL 与 FADD 以及 FasL 与 cleaved caspase 3 之间存在相关性。在相邻的正常组织中，观察到 FasL 与 Fas、FasL 与 FADD 之间存在相关性。其他标志物与性别、年龄、临床分期和生存无关联。我们的研究结果表明，这些蛋白在胃癌及其相邻正常黏膜中介导早期外在凋亡途径。FasL 蛋白与 Fas 蛋白结合，随后与死亡受体 FADD 结合，激活外在凋亡途径。在这个阶段，caspase 8 被抑制，凋亡减少。