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

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

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Abstract

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.

Original languageEnglish
Pages (from-to)1149-1159
Number of pages11
JournalOncotarget
Volume10
Issue number10
Publication statusPublished - 2019 Feb 1
Externally publishedYes

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Keywords

  • Biopsy
  • Intraclass correlation coefficient
  • Pancreatic cancer
  • Quantitative RT-PCR
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Oncology

Cite this

Ino, Y., Oguro, S., Yamazaki-Itoh, R., Hori, S., Shimada, K., & Hiraoka, N. (2019). Reliable evaluation of tumor-infiltrating lymphocytes in pancreatic cancer tissue biopsies. Oncotarget, 10(10), 1149-1159.