Research Papers:

Reliable evaluation of tumor-infiltrating lymphocytes in pancreatic cancer tissue biopsies

Yoshinori Ino _, Seiji Oguro, Rie Yamazaki-Itoh, Shutaro Hori, Kazuaki Shimada and Nobuyoshi Hiraoka

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Oncotarget. 2019; 10:1149-1159. https://doi.org/10.18632/oncotarget.26646

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Yoshinori Ino1,2, Seiji Oguro1,3,4, Rie Yamazaki-Itoh1,2, Shutaro Hori1,3,4, Kazuaki Shimada4 and Nobuyoshi Hiraoka1,2,3

1Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan

2Department of Analytical Pathology, National Cancer Center Research Institute, Tokyo, Japan

3Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan

4Hepatobiliary Pancreas Surgery Division, National Cancer Center Hospital, Tokyo, Japan

Correspondence to:

Nobuyoshi Hiraoka, email: [email protected]

Keywords: pancreatic cancer; biopsy; tumor-infiltrating lymphocytes; intraclass correlation coefficient; quantitative RT-PCR

Received: December 26, 2018     Accepted: January 21, 2019     Published: February 01, 2019


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.

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