Institute for Experimental Cancer Research, Christian-Albrechts-University, Kiel, Germany.
Department of Radiology and Neuroradiology, Christian-Albrechts-University, Kiel, Germany.
Histol Histopathol. 2019 May;34(5):491-501. doi: 10.14670/HH-18-054. Epub 2018 Oct 24.
The expression of five members of the TNF receptor superfamily and two of their ligands in human pancreatic ductal adenocarcinoma were investigated in parallel by immunohistochemistry. 41 patients with histologically confirmed ductal carcinoma of the pancreas were enrolled in this study in order (i) to compare the individual TNFR-SF expression and their ligands in PDAC-cells and (ii) to investigate their correlation with survival data. All patients had undergone pancreaticoduodenectomy and were staged as pT3N1M0. Immunostaining was done on FFPE tissue sections of the tumor tissue, using antibodies directed against TRAIL-Receptor-1, -2 and -4, TRAIL, CD95, TNF-Receptor-1 and TNF-α. The intensity and quantity of immunostaining were evaluated separately for tumor cell cytoplasm and tumor cell nucleus. Immunostaining results were correlated with each other and with patient survival. All proteins were found to be expressed in the majority of the tumor cells. The expression (i) of the following members of TNFR-SF and their ligands correlated with each other: TNF-Receptor-1 and TNFα (cytoplasmatic scores, p=0.001), TNF-Receptor 1 and TRAIL (nuclear antigen expression p=0.005 and the main score p=0.001, which contains the overall intracellular antigen expression), TNF-Receptor 1 and CD95 (main score, p=0.001), TRAIL-Receptor-1 and TRAIL-Receptor-2 (nuclear parameters, p=0.023), TRAIL-Receptor-4 and TRAIL (main score p=0.041). In addition (ii), high cytoplasmatic expression of TNF-Receptor-1 and a strong cytoplasmatic and nuclear expression of CD95 correlated significantly with a better prognosis of the PDAC patients.
通过免疫组织化学平行研究了五种 TNF 受体超家族成员及其两种配体在人胰腺导管腺癌中的表达。本研究纳入了 41 例经组织学证实的胰腺导管腺癌患者，目的是：（i）比较 PDAC 细胞中单个 TNFR-SF 表达及其配体；（ii）研究其与生存数据的相关性。所有患者均接受胰十二指肠切除术，并按分期为 pT3N1M0。使用针对 TRAIL 受体-1、-2 和 -4、TRAIL、CD95、TNF 受体-1 和 TNF-α的抗体，对肿瘤组织的 FFPE 组织切片进行免疫染色。分别评估肿瘤细胞质和肿瘤细胞核中免疫染色的强度和数量。将免疫染色结果相互关联，并与患者生存情况相关联。所有蛋白均在大多数肿瘤细胞中表达。TNFR-SF 及其配体的表达（i）相互关联：TNF 受体-1 和 TNFα（细胞质评分，p=0.001）、TNF 受体 1 和 TRAIL（核抗原表达 p=0.005 和主要评分 p=0.001，包含整体细胞内抗原表达）、TNF 受体 1 和 CD95（主要评分，p=0.001）、TRAIL 受体-1 和 TRAIL 受体-2（核参数，p=0.023）、TRAIL 受体-4 和 TRAIL（主要评分 p=0.041）。此外（ii），TNF 受体-1 的细胞质高表达和 CD95 的细胞质和核强表达与 PDAC 患者的预后显著相关。
