Reliable evaluation of tumor-infiltrating lymphocytes in pancreatic cancer tissue biopsies.
Reliable evaluation of tumor-infiltrating lymphocytes in pancreatic cancer tissue biopsies.
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DOI：
10.18632/oncotarget.26646
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发表时间：
2019-02-01
期刊：
影响因子：
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通讯作者：
Hiraoka, Nobuyoshi
中科院分区：
文献类型：
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作者：
Ino, Yoshinori;Oguro, Seiji;Hiraoka, Nobuyoshi
肿瘤浸润性淋巴细胞(TIL)代表肿瘤微环境。我们先前报道，通过免疫组织化学方法检测手术切除组织中的TIL是胰腺导管腺癌(PDAC)患者的预后指标。本研究的目的是评估如何最好地评估PDAC组织活检中的TIL。首先，我们使用241例手术切除的标本，通过定量RT-PCR(RT-qPCR)检测PDAC组织中CD3、CD4或CD8基因的表达可以预测预后。我们通过免疫组织化学和RT-qPCR的比较来评估活检组织中的TIL是否可以被有效地评估。作为研究模型，我们从手术切除的PDAC标本(n=17)中抽取了20例活检组织。我们调查了同一标本的不同活检组织中TIL的变化水平，并使用组内相关系数(ICC)进行评估。CD3、CD4和CD8的ICC值分别为0.58、0.61和0.46；这些ICC值意味着“中度”到“大量”水平的相关性。为了达到“近乎完美”，CD3、CD4和CD8分别需要进行3次、3次和5次活检。当免疫标记TIL的ICC值为“低”时，需要进行6次≥活检才能达到“中等”水平。我们发现，通过RT-qPCR和重复采样测量的TIL增加了从活检的PDAC组织中检测到的TIL的可靠性。
Tumor-infiltrating lymphocytes (TILs) represent cancer microenvironment. We previously reported TILs was prognosticators in pancreatic ductal adenocarcinoma (PDAC) patients by immunohistochemically measuring them in surgically-resected tissues. The aim of this study was to assess how best to evaluate TILs in PDAC tissue biopsies. First, we showed expression of CD3, CD4, or CD8 genes in PDAC tissue measured by quantitative RT-PCR (RT-qPCR) was prognostic using 241 surgically-resected specimens. We assessed whether the TILs in biopsied tissues can be effectively evaluated by comparing between immunohistochemistry and RT-qPCR. As a study model, we sampled twenty biopsies from surgically-resected PDAC specimen (n = 17). We investigated the variation levels of TILs in the different biopsies from the same specimen and evaluated using the intraclass correlation coefficient (ICC). The ICC value was 0.58 for CD3, 0.61 for CD4, and 0.46 for CD8, respectively; these ICC values meant correlations of "moderate" to "substantial" levels. To reach "near perfect", 3, 3, and 5 times biopsies were necessary for CD3, CD4, and CD8, respectively. When ICC values of immunolabeled TILs were of "low", ≥6 times biopsies were necessary to reach "moderate" levels. We found that TILs measured by RT-qPCR and repeated sampling increased reliability in TILs detected from biopsied PDAC tissues.