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<p>Quickly identifying driver gene mutations in solid cancers is important. However, next-generation sequencing (NGS)-based mutation detection methods are time-consuming and expensive. Peptide nucleic acid (PNA) probe-based mutant mRNA detection systems are quick and inexpensive. We previously demonstrated that epidermal growth factor receptor (EGFR)-mutations were efficiently visualized in formalin-fixed paraffin-embedded (FFPE) specimens from transplanted non-small cell lung cancer (NSCLC) tumors using an EGFR mutation-specific PNA:DNA probe. Herein, the efficiency of PNA:DNA probes in detecting EGFR-mutations in FFPE specimens from patients with NSCLC and the colocalization of EGFR-mutations with tumor-infiltrating lymphocyte (TIL) status were determined. The EGFR mutation L858R-specific PNA:DNA probe detected heterogeneously localized mutations with a sensitivity similar to detection with the anti-L858R antibody. TIL analysis of L858R-mutated tumors revealed that CD8<sup>+</sup>PD-1<sup>+</sup> T cells and CD68<sup>+</sup> macrophages were scarce in tumors, but in the cytokeratin-positive intra-tumoral regions, CD4<sup>+</sup>, FoxP3<sup>+</sup>, and CD204<sup>+</sup> cells tended to be more abundant in the L858R-positive tumor area than in the negative area. Thus, PNA:DNA probes specific for EGFR-mutations can detect areas with heterogeneous EGFR mutants in whole cancer tissues and can be used to evaluate the mutation-associated TIL status in EGFR-mutant cancer tissues.</p>

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Localization of epidermal growth factor receptor-mutations using PNA:DNA probes in clinical specimens from patients with non-small cell lung cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月2日

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  • Haruo Miyata,
  • Hajime Shigeto,
  • Tomoatsu Ikeya,
  • Tadashi Ashizawa,
  • Akira Iizuka,
  • Yasufumi Kikuchi,
  • Chie Maeda,
  • Akari Kanematsu,
  • Kazue Yamashita,
  • Kenichi Urakami,
  • Yuji Shimoda,
  • Takeshi Nagashima,
  • Keiichi Ohshima,
  • Yasuhisa Ohde,
  • Mitsuhiro Isaka,
  • Takashi Sugino,
  • Koji Muramatsu,
  • Hirotsugu Kenmotsu,
  • Toshiaki Takahashi,
  • Ken Yamaguchi,
  • Mizuki Kitamatsu,
  • Shohei Yamamura,
  • Yasuto Akiyama

摘要

Quickly identifying driver gene mutations in solid cancers is important. However, next-generation sequencing (NGS)-based mutation detection methods are time-consuming and expensive. Peptide nucleic acid (PNA) probe-based mutant mRNA detection systems are quick and inexpensive. We previously demonstrated that epidermal growth factor receptor (EGFR)-mutations were efficiently visualized in formalin-fixed paraffin-embedded (FFPE) specimens from transplanted non-small cell lung cancer (NSCLC) tumors using an EGFR mutation-specific PNA:DNA probe. Herein, the efficiency of PNA:DNA probes in detecting EGFR-mutations in FFPE specimens from patients with NSCLC and the colocalization of EGFR-mutations with tumor-infiltrating lymphocyte (TIL) status were determined. The EGFR mutation L858R-specific PNA:DNA probe detected heterogeneously localized mutations with a sensitivity similar to detection with the anti-L858R antibody. TIL analysis of L858R-mutated tumors revealed that CD8+PD-1+ T cells and CD68+ macrophages were scarce in tumors, but in the cytokeratin-positive intra-tumoral regions, CD4+, FoxP3+, and CD204+ cells tended to be more abundant in the L858R-positive tumor area than in the negative area. Thus, PNA:DNA probes specific for EGFR-mutations can detect areas with heterogeneous EGFR mutants in whole cancer tissues and can be used to evaluate the mutation-associated TIL status in EGFR-mutant cancer tissues.